Understanding how atherosclerosis and angioplasty biomechanically affect the coronary artery wall is crucial for comprehending the pathophysiology of this disease and advancing potential treatments. However, acquiring this information experimentally or in vivo presents challenges. To overcome this, different computational methods have been employed. This research assessed the impact of atherosclerosis and angioplasty on the strains of each coronary artery tunic using the finite element method.

Anatomical data were used to create two three-dimensional models of the left anterior descending coronary artery: one representing a normal artery and the other with concentric atherosclerosis, which included the surrounding epicardial fat tissue (EFT) and the three arterial tunics (e.g., intima, media, and adventitia). Blood pressure was applied to both models, and angioplasty was performed in the atherosclerotic model. The mean maximum principal and minimum principal strains were obtained for each layer in each case, and the impact of EFT was analyzed by comparing the results of including and omitting it. Furthermore, a sensitivity analysis was conducted for EFT stiffness, EFT volume, and blood pressure.

Noteworthy biomechanical alterations were observed in the atherosclerotic model before and after angioplasty, compared to the healthy state. After angioplasty, strains in the media and adventitia layers increased on average by up to fivefold, whereas the intima layer experienced a comparatively lower impact. Similarly, excluding EFT resulted in an average fourfold increase in strains in the tunics of both the healthy and atherosclerotic models. In addition, in both healthy and atherosclerotic models, a rise in blood pressure caused the most significant increase in arterial tunic strains, followed by reduced EFT stiffness and increased EFT volume, in order of impact.

Coronary artery wall strains are significantly altered by atherosclerosis and angioplasty, leading to cellular growth in the media and adventitia layers and subsequent reobstruction of the lumen after the procedure. EFT strongly influences coronary wall biomechanics, with low EFT stiffness and high volume predicted as risk factors for the development and severity of atherosclerosis. However, all the above may be modulated through interventions targeting epicardial adipose tissue.

Little is known about the association between periprocedural hemodynamics and in-stent restenosis (ISR) following stent implantation in patients with symptomatic intracranial atherosclerotic stenosis (ICAS). This study aims to identify periprocedural hemodynamics that may be associated with ISR. Subjects were selected from the NOVA trial (The First-in-man Trial Evaluating the Safety and Efficacy of the NOVA Intracranial Stent Trial). ISR was defined as greater than 50% stenosis of the luminal diameter within or immediately adjacent to (within 5 mm) the implanted stent. Periprocedural hemodynamics, including cerebral blood flow, cerebral blood volume, mean transit time, and time to peak (TTP), were derived from the time-density curve generated from digital subtraction angiography using the fast Fourier transform algorithm. Of the 263 patients enrolled in the NOVA trial, 176 with symptomatic high-grade ICAS who underwent stent implantation were included in this study. Of these, 35 (19.9%) were diagnosed with ISR at the one-year follow-up. No significant differences in pre-procedure hemodynamics were observed between stent groups and between the ISR groups and the non-ISR group. Higher post-procedure TTP (OR, 1.95; 95% CI, 1.26-3.02), the use of bare-metal stents (OR, 5.40; 95% CI, 2.21-13.19), and higher post-procedure residual stenosis (OR, 1.08; 95% CI, 1.03-1.13) were independent factors associated with ISR. Higher post-procedure TTP, the use of bare-metal stents, and higher post-procedure residual stenosis were independent factors associated with ISR. The combined use of periprocedural hemodynamics and clinical factors may help predict ISR in patients with symptomatic high-grade ICAS.

The regeneration of endothelial cells (ECs) lining arteries, veins, and large lymphatic vessels plays an important role in vascular pathology. To understand the mechanisms of atherogenesis, it is important to determine what happens during endothelial regeneration. A comparison of these processes in the above-mentioned vessels reveals both similarities and some significant differences. Regeneration is carried out by moving intact ECs from the edges of the viable endothelial layer towards the centre of the EC damage zone. A sharp decrease in contact inhibition leads to the spreading of the edges of the ECs situated on the damage border. This stimulates the second row of ECs to enter the S-phase, then the G2 phase of cell cycle, and finally mitosis. In all three types of vessels studied, mitotically dividing ECs were found using correlation light and electron microscopy. These ECs have a body protruding into the lumen of the vessel, covered with micro-villi and other outgrowths. The level of EC rounding and protruding is highest in the arteries and least pronounced in the lymphatic vessels. The intercellular contacts of mitotically dividing cells become wider. The EC division leads to an increase in the density of ECs. ECs moving over the damaged area and partially outside the damaged area acquire a fusiform shape. In the process of regeneration of arterial endothelium, the damaged ECs are removed. Then health ECs move to a surface devoid of endothelium, and detach spreading out, flattened platelets from the luminal surface of the vessel. In the veins, ECs grow on the surface of platelets and microthrombi. In lymphatic vessels, ECs detach from the basement membrane slower than in the veins and arteries. There, the migrating ECs grow under fibrin fibres. After some time (usually after 30 days), the EC mosaic returns to normal in all three types of vessels.

Vascular stent intervention is a pivotal treatment for coronary atherosclerosis, though in-stent thrombosis remains a significant postoperative complication with an unclear underlying mechanism. This study utilized dissipated particle dynamics analysis to investigate the impact of stent and its injury on platelet behavior. The findings suggest that thrombus formation upstream of the stent is mainly initiated by upstream arterial injury, which leads to increased platelet accumulation and activation in that area. While thrombosis downstream of the stent is more directly influenced by the stent itself. The morphology and size of in-stent thrombosis can vary significantly due to the different contributions of the stent and underlying injuries. Additionally, the volume of in-stent thrombosis is affected by the extent of the injury and the viscosity of platelets, showing a notable increase in volume with the lengthening of the injury area and rise in platelet viscosity. This study provides a novel theoretical framework for optimizing stent placement strategies and structural designs by examining the effects of stent struts and associated injuries on thrombus formation.

Over the last decade, several in vivo and computational investigations have significantly advanced our understanding of the pathophysiology of coronary bifurcations, contributing to the enhancement of their percutaneous revascularization. The carina of the coronary bifurcations plays a substantial role in generating their main hemodynamic features, including distinctive flow patterns with secondary flows and specific shear stress patterns. These factors play a pivotal role in determining the susceptibility, development, and progression of atherosclerosis. The underlying pathophysiological mechanisms of atherosclerosis in coronary bifurcations are complex and multifactorial. Understanding these mechanisms is fundamental to comprehending lesions at the bifurcation level and informing future treatment strategies. This review aims to present the currently available data regarding the pathophysiological and prognostic role of the carina in coronary bifurcations, offering an interpretation of these findings from the perspective of interventional cardiologists, providing valuable insights for their clinical practice.

Vascular injury is central to the pathogenesis and progression of cardiovascular diseases, however, fostering alternative strategies to alleviate vascular injury remains a persisting challenge. Given the central role of cell-derived nitric oxide (NO) in modulating the endogenous repair of vascular injury, NO-generating proteolipid nanovesicles (PLV-NO) are designed that recapitulate the cell-mimicking functions for vascular repair and replacement. Specifically, the proteolipid nanovesicles (PLV) are versatilely fabricated using membrane proteins derived from different types of cells, followed by the incorporation of NO-generating nanozymes capable of catalyzing endogenous donors to produce NO. Taking two vascular injury models, two types of PLV-NO are tailored to meet the individual requirements of targeted diseases using platelet membrane proteins and endothelial membrane proteins, respectively. The platelet-based PLV-NO (pPLV-NO) demonstrates its efficacy in targeted repair of a vascular endothelium injury model through systemic delivery. On the other hand, the endothelial cell (EC)-based PLV-NO (ePLV-NO) exhibits suppression of thrombosis when modified onto a locally transplanted small-diameter vascular graft (SDVG). The versatile design of PLV-NO may enable a promising therapeutic option for various vascular injury-evoked cardiovascular diseases.

Vasculopathy is the most common complication of diabetes. Endothelial cells located in the innermost layer of blood vessels are constantly affected by blood flow or vascular components; thus, their mechanosensitivity plays an important role in mediating vascular regulation. Endothelial damage, one of the main causes of hyperglycemic vascular complications, has been extensively studied. However, the role of mechanosensitive signaling in hyperglycemic endothelial damage remains unclear.

Vascular endothelial-specific Piezo1 knockout mice were generated to investigate the effects of Piezo1 on Streptozotocin-induced hyperglycemia and vascular endothelial injury. In vitro activation or knockdown of Piezo1 was performed to evaluate the effects on the proliferation, migration, and tubular function of human umbilical vein endothelial cells in high glucose. Reactive oxygen species production, mitochondrial membrane potential alternations, and oxidative stress-related products were used to assess the extent of oxidative stress damage caused by Piezo1 activation.

Our study found that in VECreERT2;Piezo1flox/flox mice with Piezo1 conditional knockout in vascular endothelial cells, Piezo1 deficiency alleviated streptozotocin-induced hyperglycemia with reduced apoptosis and abscission of thoracic aortic endothelial cells, and decreased the inflammatory response of aortic tissue caused by high glucose. Moreover, the knockout of Piezo1 showed a thinner thoracic aortic wall, reduced tunica media damage, and increased endothelial nitric oxide synthase expression in transgenic mice, indicating the relief of endothelial damage caused by hyperglycemia. We also showed that Piezo1 activation aggravated oxidative stress injury and resulted in severe dysfunction through the Ca2+-induced CaMKII-Nrf2 axis in human umbilical vein endothelial cells. In Piezo1 conditional knockout mice, Piezo1 deficiency partially restored superoxide dismutase activity and reduced malondialdehyde content in the thoracic aorta. Mechanistically, Piezo1 deficiency decreased CaMKII phosphorylation and restored the expression of Nrf2 and its downstream molecules HO-1 and NQO1.

In summary, our study revealed that Piezo1 is involved in high glucose-induced oxidative stress injury and aggravated endothelial dysfunction, which have great significance for alleviating endothelial damage caused by hyperglycemia.

Despite advances in pharmacotherapy and device innovation, in-stent restenosis (ISR) and stent thrombosis (ST) remain serious complications following percutaneous coronary intervention (PCI) procedure with stent implantation. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an enzyme involved in plasma cholesterol homeostasis and recently emerged as a therapeutic target for hypercholesterolemia. Antibody-based PCSK9 inhibition is increasingly used in different subsets of patients, including those undergoing PCI. However, whether PCSK9 inhibition affects outcome after stent implantation remains unknown.

12 to 14 weeks old C57Bl/6 mice underwent carotid artery bare-metal stent implantation. Compared to sham intervention, stent implantation was associated with increased expression of several inflammatory mediators, including PCSK9. The increase in PCSK9 protein expression was confirmed in the stented vascular tissue, but not in plasma. To inhibit PCSK9, alirocumab was administered weekly to mice before stent implantation. After 6 weeks, histological examination revealed increased intimal hyperplasia in the stented segment of alirocumab-treated animals compared to controls. In vitro, alirocumab promoted migration and inhibited the onset of senescence in primary human vascular smooth muscle cells (VSMC). Conversely, it blunted the migration and increased the senescence of endothelial cells (EC).

Antibody-based PCSK9 inhibition promotes in-stent intimal hyperplasia and blunts vascular healing by increasing VSMC migration, while reducing that of EC. This effect is likely mediated, at least in part, by a differential effect on VSMC and EC senescence. The herein-reported data warrant additional investigations concerning the use of PCSK9 inhibitors in patients undergoing PCI with stent implantation.

Cardiovascular metal stents have shown potential in the treatment of coronary artery disease using percutaneous coronary intervention. However, thrombosis, endothelialization, and new atherosclerosis after stent implantation remain unsolved problems. Herein, a multifunctional coating material based on phase-transited lysozyme was developed to promote stent endothelialization and simultaneously reduce thrombus events by embedding moieties of heparin and co-immobilized copper ions for in-situ catalyzing nitric oxide (NO) generation. The lysozyme-based biomimetic coating is compatible with blood and enables facile loading and sustainable release of copper ions to produce NO with donors via catalytic reaction. The novel coating strategy displayed several bio-effects of anti-thrombosis; it synergistically promoted endothelial cell growth and inhibited smooth muscle cell growth. Thus, this systemic in vitro study will provide a foundation for developing multifunctional cardiovascular stents in clinical settings.

Computational fluid dynamics (CFD) is emerging as an effective technology able to improve procedural outcomes and enhance clinical decision-making in patients with coronary artery disease (CAD). The present study aims to assess the state of knowledge, use and clinical acceptability of CFD in the diagnosis and treatment of CAD.

We realized a 20-questions international, anonymous, cross-sectional survey to cardiologists to test their knowledge and confidence on CFD as a technology applied to patients suffering from CAD. Responses were recorded between May 18, 2022, and June 12, 2022.

A total of 466 interventional cardiologists (mean age 48.4 ± 8.3 years, males 362), from 42 different countries completed the survey, for a response rate of 45.9%. Of these, 66.6% declared to be familiar with the term CFD, especially for optimization of existing interventional techniques (16.1%) and assessment of hemodynamic quantities related with CAD (13.7%). About 30% of respondents correctly answered to the questions exploring their knowledge on the pathophysiological role of some CFD-derived quantities such as wall shear stress and helical flow in coronary arteries. Among respondents, 85.9% would consider patient-specific CFD-based analysis in daily interventional practice while 94.2% declared to be interested in receiving a brief foundation course on the basic CFD principles. Finally, 87.7% of respondents declared to be interested in a cath-lab software able to conduct affordable CFD-based analyses at the point-of-care.

Interventional cardiologists reported to be profoundly interested in adopting CFD simulations as a technology supporting decision making in the treatment of CAD in daily practice.

Intimal hyperplasia (IH) represents a major challenge following cardiovascular interventions. While mechanisms are poorly understood, the inefficient preventive methods incentivize the search for novel therapies. A vessel-on-a-dish platform is presented, consisting of direct-contact cocultures with human primary endothelial cells (ECs) and smooth muscle cells (SMCs) exposed to both laminar pulsatile and disturbed flow on an orbital shaker. With contractile SMCs sitting below a confluent EC layer, a model that successfully replicates the architecture of a quiescent vessel wall is created. In the novel IH model, ECs are seeded on synthetic SMCs at low density, mimicking reendothelization after vascular injury. Over 3 days of coculture, ECs transition from a network conformation to confluent 2D islands, as promoted by pulsatile flow, resulting in a "defected" EC monolayer. In defected regions, SMCs incorporated plasma fibronectin into fibers, increased proliferation, and formed multilayers, similarly to IH in vivo. These phenomena are inhibited under confluent EC layers, supporting therapeutic approaches that focus on endothelial regeneration rather than inhibiting proliferation, as illustrated in a proof-of-concept experiment with Paclitaxel. Thus, this in vitro system offers a new tool to study EC-SMC communication in IH pathophysiology, while providing an easy-to-use translational disease model platform for low-cost and high-content therapeutic development.

Background The endothelium is essential for maintaining vascular physiological homeostasis and the endothelial injury leads to the neointimal hyperplasia because of the excessive proliferation of vascular smooth muscle cells. Endothelial Foxp1 (forkhead box P1) has been shown to control endothelial cell (EC) proliferation and migration in vitro. However, whether EC-Foxp1 participates in neointimal formation in vivo is not clear. Our study aimed to investigate the roles and mechanisms of EC-Foxp1 in neointimal hyperplasia. Methods and Results The wire injury femoral artery neointimal hyperplasia model was performed in Foxp1 EC-specific loss-of-function and gain-of-function mice. EC-Foxp1 deletion mice displayed the increased neointimal formation through elevation of vascular smooth muscle cell proliferation and migration, and the reduction of EC proliferation hence reendothelialization after injury. In contrast, EC-Foxp1 overexpression inhibited the neointimal formation. EC-Foxp1 paracrine regulated vascular smooth muscle cell proliferation and migration via targeting matrix metalloproteinase-9. Also, EC-Foxp1 deletion impaired EC repair through reduction of EC proliferation via increasing cyclin dependent kinase inhibitor 1B expression. Delivery of cyclin dependent kinase inhibitor 1B-siRNA to ECs using RGD (Arg-Gly-Asp)-peptide magnetic nanoparticle normalized the EC-Foxp1 deletion-mediated impaired EC repair and attenuated the neointimal formation. EC-Foxp1 regulates matrix metalloproteinase-9/cyclin dependent kinase inhibitor 1B signaling pathway to control injury induced neointimal formation. Conclusions Our study reveals that targeting EC-Foxp1-matrix metalloproteinase-9/cyclin dependent kinase inhibitor 1B pathway might provide future novel therapeutic interventions for restenosis.

Coronary artery stents have profound effects on arterial function by altering fluid flow mass transport and wall shear stress. We developed a new integrated methodology to analyse the effects of stents on mass transport and shear stress to inform the design of haemodynamically-favourable stents.

Stents were deployed in model vessels followed by tracking of fluorescent particles under flow. Parallel analyses involved high-resolution micro-computed tomography scanning followed by computational fluid dynamics simulations to assess wall shear stress distribution. Several stent designs were analysed to assess whether the workflow was robust for diverse strut geometries. Stents had striking effects on fluid flow streamlines, flow separation or funnelling, and the accumulation of particles at areas of complex geometry that were tightly coupled to stent shape. CFD analysis revealed that stents had a major influence on wall shear stress magnitude, direction and distribution and this was highly sensitive to geometry.

Integration of particle tracking with CFD allows assessment of fluid flow and shear stress in stented arteries in unprecedented detail. Deleterious flow perturbations, such as accumulation of particles at struts and non-physiological shear stress, were highly sensitive to individual stent geometry. Novel designs for stents should be tested for mass transport and shear stress which are important effectors of vascular health and repair.

MicroRNAs (miRNA) are major regulators of intercellular communication and key players in the pathophysiology of cardiovascular disease. This study aimed to determine the miRNA fingerprint in a cohort of 53 patients with acute myocardial infarction (AMI) with non-ST-segment elevation (NSTEMI) relative to miRNA expression in healthy controls (n = 51). miRNA expression was initially profiled by miRNA array in the serum of patients undergoing cardiac catheterization during NSTEMI (n = 8) and 1 year past the event (follow-up, n = 8) and validated in the entire cohort. In total, 58 miRNAs were differentially expressed during AMI (p < 0.05), while 36 were modified at follow-up (Fisher’s exact test: p = 0.0138). Enrichment analyses revealed differential regulation of biological processes by miRNA at each specific time point (AMI vs. follow-up). During AMI, the miRNA profile was associated mainly with processes involved in vascular development. However, 1 year after AMI, changes in miRNA expression were partially related to the regulation of cardiac tissue morphogenesis. Linear correlation analysis of miRNA with serum levels of cytokines and chemokines revealed that let-7g-5p, let-7e-5p, and miR-26a-5p expression was inversely associated with serum levels of pro-inflammatory cytokines TNF-α, and the chemokines MCP-3 and MDC. Transient transfection of human endothelial cells (HUVEC) with let-7e-5p inhibitor or mimic demonstrated a key role for this miRNA in endothelial function regulation in terms of cell adhesion and angiogenesis capacity. HUVEC transfected with let-7e-5p mimic showed a 20% increase in adhesion capacity, whereas transfection with let-7e-5p inhibitor increased the number of tube-like structures. This study pinpoints circulating miRNA expression fingerprint in NSTEMI patients, specific to the acute event and changes at 1-year follow-up. Additionally, given its involvement in modulating endothelial cell function and vascularization, altered let-7e-5p expression may constitute a therapeutic biomarker and target for ischemic heart disease.

Despite the important advancements in the stent technology for the treatment of diseased coronary arteries, major complications still affect the post-operative long-term outcome. The stent-induced flow disturbances, and especially the altered wall shear stress (WSS) profile at the strut level, play an important role in the pathophysiological mechanisms leading to stent thrombosis (ST) and in-stent restenosis (ISR). In this context, the analysis of the WSS topological skeleton is gaining more and more interest by extending the current understanding of the association between local hemodynamics and vascular diseases. The present study aims to analyze the impact that a deployed coronary stent has on the WSS topological skeleton. Computational fluid dynamics simulations were performed in three stented human coronary artery geometries reconstructed from clinical images. The selected cases presented stents with different designs (i.e., two contemporary drug eluting stents and one bioresorbable scaffold) and included regions with stent malapposition or overlapping. A recently proposed Eulerian-based approach was applied to analyze the WSS topological skeleton features. The results highlighted that the presence of single or multiple stents within a coronary artery markedly impacts the WSS topological skeleton. In particular, repetitive patterns of WSS divergence were observed at the luminal surface, highlighting a WSS contraction action proximal to the struts and a WSS expansion action distal to the struts. This WSS action pattern was independent from the stent design. In conclusions, these findings could contribute to a deeper understanding of the hemodynamic-driven processes underlying ST and ISR.

Stent thrombosis (ST) carries a high risk of myocardial infarction and death. Lack of endothelial coverage is an important prognostic indicator of ST after stenting. While stent strut thickness is a critical factor in ST, a mechanistic understanding of its effect is limited and the role of haemodynamics is unclear. Endothelialization was tested using a wound-healing assay and five different stent strut models ranging in height between 50 and 150 µm for circular arc (CA) and rectangular (RT) geometries and a control without struts. Under static conditions, all stent strut surfaces were completely endothelialized. Reversing pulsatile disturbed flow caused full endothelialization, except for the stent strut surfaces of the 100 and 150 µm RT geometries, while fully antegrade pulsatile undisturbed flow with a higher mean wall shear stress caused only the control and the 50 µm CA geometries to be fully endothelialized. Modest streamlining and decrease in height of the stent struts improved endothelial coverage of the peri-strut and stent strut surfaces in a haemodynamics dependent manner. This study highlights the impact of the stent strut height (thickness) and geometry (shape) on the local haemodynamics, modulating reendothelialization after stenting, an important factor in reducing the risk of stent thrombosis.

Stents are scaffolding cardiovascular implants used to restore blood flow in narrowed arteries. However, the presence of the stent alters local blood flow and shear stresses on the surrounding arterial wall, which can cause adverse tissue responses and increase the risk of adverse outcomes. There is a need for optimization of stent designs for hemodynamic performance. We used multi-objective optimization to identify ideal combinations of design variables by assessing potential trade-offs based on common hemodynamic indices associated with clinical risk and mechanical performance of the stents. We studied seven design variables including strut cross-section, strut dimension, strut angle, cell alignment, cell height, connector type and connector arrangement. Optimization objectives were the percentage of vessel area exposed to adversely low time averaged WSS (TAWSS) and adversely high Wall Shear Stress (WSS) assessed using computational fluid dynamics modeling, as well as radial stiffness of the stent using FEA simulation. Two multi-objective optimization algorithms were used and compared to iteratively predict ideal designs. Out of 50 designs, three best designs with respect to each of the three objectives, and two designs in regard to overall performance were identified.

Flow diverters (FDs) are an effective treatment for intracranial aneurysms, though not free from hemorrhagic complications. A previous study demonstrated increased vascular contractility after FD-implantation as a potential mechanism of distal complications. Our study aimed to investigate whether L-arginine medication affects vascular contractility following FD deployment in a rabbit model.

FDs were implanted in the aorta of normal rabbits (+FD, n = 10), with sham-operated aorta as controls (n = 5). L-Arginine was given in the drinking water (2.25% L-arginine hydrochloride) of half of the +FD animals (+FD/+Arg). Force contraction vascular contractility studies were performed on the aortic rings proximal and distal to the FD using an organ bath. Total eNOS, eNOS(pS1177), eNOS(pT495), COX-2, and S100A4 were quantified by western analysis on total protein lysates from aortic segments, normalizing to GAPDH.

Mean vascular contractility was 53% higher in distal relative to proximal aortic segments (P = 0.0038) in +FD animals, but were not significantly different in +FD/+Arg animals, or in sham-operated controls. The +FD animals expressed significantly reduced levels of eNOS(pS1177) than sham-operated controls (P = 0.0335), while both the +FD and +FD/+Arg groups had reduced levels of eNOS(pT495) relative to sham-operated controls (P = 0.0331 and P = 0.0311, respectively).

These results suggest that L-arginine medication reduces distal vascular contractility after FD treatment via nitric oxide production and thus might mitigate risk for downstream complications.

[Figure: see text].

Coronary stents are deployed to treat the coronary artery disease (CAD) by reopening stenotic regions in arteries to restore blood flow, but the risk of the in-stent restenosis (ISR) is high after stent implantation. One of the reasons is that stent implantation induces changes in local hemodynamic environment, so it is of vital importance to study the blood flow in stented arteries. Based on regarding the red blood cell (RBC) as a rigid solid particle and regarding the blood (including RBCs and plasma) as particle suspensions, a non-Newtonian particle suspensions model is proposed to simulate the realistic blood flow in this work. It considers the blood's flow pattern and non-Newtonian characteristic, the blood cell-cell interactions, and the additional effects owing to the bi-concave shape and rotation of the RBC. Then, it is compared with other four common hemodynamic models (Newtonian single-phase flow model, Newtonian Eulerian two-phase flow model, non-Newtonian single-phase flow model, non-Newtonian Eulerian two-phase flow model), and the comparison results indicate that the models with the non-Newtonian characteristic are more suitable to describe the realistic blood flow. Afterwards, based on the non-Newtonian particle suspensions model, the local hemodynamic environment in stented arteries is investigated. The result shows that the stent strut protrusion into the flow stream would be likely to produce the flow stagnation zone. And the stent implantation can make the pressure gradient distribution uneven. Besides, the wall shear stress (WSS) of the region adjacent to every stent strut is lower than 0.5 Pa, and along the flow direction, the low-WSS zone near the strut behind is larger than that near the front strut. What's more, in the regions near the struts in the proximal of the stent, the RBC particle stagnation zone is easy to be formed, and the erosion and deposition of RBCs are prone to occur. These hemodynamic analyses illustrate that the risk of ISR is high in the regions adjacent to the struts in the proximal and the distal ends of the stent when compared with struts in other positions of the stent. So the research can provide a suggestion on the stent design, which indicates that the strut structure in these positions of a stent should be optimized further.

Shape memory materials have been successfully applied to minimally invasive implantation of medical devices. However, organ-movement-specific shape programing at a microscale level has never been demonstrated despite significant unmet needs. As vein-to-artery grafting induces vein dilation and stenosis, a polymeric self-enclosable external support (SES) is designed to wrap the vascular out-wall. Its micropores are programmed to increase sizes and interconnections upon dilation. Vessel dilation promotes venous maturation, but overdilation induces stenosis by disturbed blood flow. Therefore, the unique elastic shape-fixity of SES provides a foundation to enable a stable microscale shape transition by maintaining the vein dilation. The shape transition of micropore architecture upon dilation induces beneficial inflammation, thereby regenerating vasa vasorum and directing smooth muscle cell migration toward adventitia with the consequent muscle reinforcement of veins. This game-changer approach prevents the stenosis of vein-to-artery grafting by rescuing ischemic disorders and promoting arterial properties of veins.

In-stent restenosis (ISR) is the major drawback of superficial femoral artery (SFA) stenting. Abnormal hemodynamics after stent implantation seems to promote the development of ISR. Accordingly, this study aims to investigate the impact of local hemodynamics on lumen remodeling in human stented SFA lesions. Ten SFA models were reconstructed at 1-week and 1-year follow-up from computed tomography images. Patient-specific computational fluid dynamics simulations were performed to relate the local hemodynamics at 1-week, expressed in terms of time-averaged wall shear stress (TAWSS), oscillatory shear index and relative residence time, with the lumen remodeling at 1-year, quantified as the change of lumen area between 1-week and 1-year. The TAWSS was negatively associated with the lumen area change (ρ = - 0.75, p = 0.013). The surface area exposed to low TAWSS was positively correlated with the lumen area change (ρ = 0.69, p = 0.026). No significant correlations were present between the other hemodynamic descriptors and lumen area change. The low TAWSS was the best predictive marker of lumen remodeling (positive predictive value of 44.8%). Moreover, stent length and overlapping were predictor of ISR at follow-up. Despite the limited number of analyzed lesions, the overall findings suggest an association between abnormal patterns of WSS after stenting and lumen remodeling.

The fervency for advancement and evolution in percutaneous coronary intervention has revolutionised the treatment of coronary artery disease. Historically, the focus of the interventional cardiologist was directed at the restoration of luminal patency of the major epicardial coronary arteries, yet whilst this approach is evolving with much greater utilisation of physiological assessment, it often neglects consideration of the role of the coronary microcirculation, which has been shown to clearly influence prognosis. In this review, we explore the narrative of the coronary circulation as more than just a simple conduit for blood but an organ with functional significance. We review organisation and physiology of the coronary circulation, as well as the current methods and techniques used to examine it. We discuss the studies exploring coronary artery endothelial function, appreciating that coronary artery disease occurs on a spectrum of disorder and that percutaneous coronary intervention has a latent effect on the coronary circulation with long-term consequences. It is concluded that greater recognition of the coronary artery endothelium and mechanisms of the coronary circulation should further guide revascularisation strategies.

Bioresorbable scaffold (BRS) regions exposed to flow recirculation, low time-averaged wall shear stress (TAWSS) and high oscillatory shear index (OSI) develop increased neointima tissue. We investigated haemodynamic features in four different BRSs.

Fantom (strut height [SH] = 125 µm), Fantom Encore (SH = 98 µm), Absorb (SH = 157 µm) and Magmaris (SH = 150 µm) BRSs were deployed in phantom tubes and imaged with microCT. Both 2D and 3D geometrical scaffold models were reconstructed. Computational fluid dynamics (CFD) simulation was performed to compute TAWSS and OSI. Thicker struts had larger recirculation zones and lower TAWSS in 2D. Absorb had the largest recirculation zone and the lowest TAWSS (240 µm and -0.18 Pa), followed by Magmaris (170 µm and -0.15 Pa), Fantom (140 µm and -0.14 Pa) and Fantom Encore (100 µm and -0.13 Pa). Besides strut size, stent design played a dominant role in 3D. The highest percentage area adverse TAWSS (<0.5 Pa) and OSI (>0.2) were found for Fantom (56% and 30%) and Absorb (53% and 33%), followed by Fantom Encore (30% and 25%) and Magmaris (25% and 20%). Magmaris had the smallest areas due to a small footprint and rounded struts.

Due to stent design, both Fantom Encore and Magmaris showed smaller TAWSS and OSI than Fantom and Absorb. This study quantifies which scaffold features are most important to reduce long-term restenosis.

Endothelial barrier integrity is required for maintaining vascular homeostasis and fluid balance between the circulation and surrounding tissues and for preventing the development of vascular disease. Despite comprehensive understanding of the molecular mechanisms and signaling pathways that mediate endothelial injury, the regulatory mechanisms responsible for endothelial regeneration and vascular repair are incompletely understood and constitute an emerging area of research. Endogenous and exogenous reparative mechanisms serve to reverse vascular damage and restore endothelial barrier function through regeneration of a functional endothelium and re-engagement of endothelial junctions. In this review, mechanisms that contribute to endothelial regeneration and vascular repair are described. Targeting these mechanisms has the potential to improve outcome in diseases that are characterized by vascular injury, such as atherosclerosis, restenosis, peripheral vascular disease, sepsis, and acute respiratory distress syndrome. Future studies to further improve current understanding of the mechanisms that control endothelial regeneration and vascular repair are also highlighted.

The optimal position of the balloon distal radio-opaque marker during the post optimization technique (POT) remains debated. We analyzed three potential different balloon positions for the final POT in two different two-stenting techniques, to compare the hemodynamic effects in terms of wall shear stress (WSS) in patients with complex left main (LM) coronary bifurcation.

We reconstructed the patient-specific coronary bifurcation anatomy using the coronary computed tomography angiography (CCTA) data of 8 consecutive patients (6 males, mean age 68.2± 18.6 years) affected by complex LM bifurcation disease. Subsequently a virtual bench test was performed in each patient using two different double stenting techniques represented by the DK and Nano crush using the reconstruction of Orsiro stents (Biotronik IC, Bulack, Switzerland).

A significant reduction in the mean WSS values in all the lesion's sites was observed when the final POT was performed 1 mm distally the carina cut plane in both techniques. Moreover, a significant improvement in the mean WSS values of the entire SB (e.g. LCX) was obtained performing the POT 1 mm distally to the carina cut plane. The proximal POT resulted in larger area of lower WSS values at the carina using both the Nano crush and the DK crush techniques.

In patients with complex LM bifurcation disease the use of a final POT performed 1 mm distally to the carina cut plane might results in more favorable WSS patterns (i.e. higher WSS values) along all stented segments and, especially, along the entire LCX lesions.

Percutaneous coronary intervention for coronary artery disease treatment often results in pathological vascular injury, characterized by P-selectin overexpression. Adipose-derived stem cells (ADSCs) therapeutic efficacy remains elusive due to poor ADSCs targeting and retention in injured vessels. Here, conjugated P-selectin binding peptide (PBP) to polyethylene glycol-conjugated phospholipid derivative (DMPE-PEG) linkers (DMPE-PEG-PBP; DPP) are used to facilitate the modification of PBP onto ADSCs cell surfaces via hydrophobic interactions between DMPE-PEG and the phospholipid bilayer. DPP modification neither has influence on ADSCs proliferation nor apoptosis/paracrine factor gene expression. A total of 5 × 10-6 m DPP-modified ADSCs (DPP-ADSCs) strongly binds to P-selectin-displaying activated platelets and endothelial cells (ECs) in vitro and to wire-injured rat femoral arteries when administered by intra-arterial injection. Targeted binding of ADSCs shields injury sites from platelet and leukocyte adhesion, thereby decreasing inflammation at injury sites. Furthermore, targeted binding of ADSCs recovers injured ECs functionality and reduces platelet-initiated vascular smooth muscle cells (VSMCs) chemotactic migration. Targeted binding of DPP-human ADSCs to balloon-injured human femoral arteries is also demonstrated in ex vivo experiments. Overall, DPP-ADSCs promote vascular repair, inhibit neointimal hyperplasia, increase endothelium functionality, and maintain normal VSMCs alignment, supporting preclinical noninvasive utilization of DPP-ADSCs for vascular injury.

Atherosclerosis and vascular disease of larger arteries are often associated with hypoxia within the layers of the vascular wall. In this review, we begin with a brief overview of the molecular changes in vascular cells associated with hypoxia and then emphasize the transport mechanisms that bring oxygen to cells within the vascular wall. We focus on fluid mechanical factors that control oxygen transport from lumenal blood flow to the intima and inner media layers of the artery, and solid mechanical factors that influence oxygen transport to the adventitia and outer media via the wall's microvascular system-the vasa vasorum (VV). Many cardiovascular risk factors are associated with VV compression that reduces VV perfusion and oxygenation. Dysfunctional VV neovascularization in response to hypoxia contributes to plaque inflammation and growth. Disturbed blood flow in vascular bifurcations and curvatures leads to reduced oxygen transport from blood to the inner layers of the wall and contributes to the development of atherosclerotic plaques in these regions. Recent studies have shown that hypoxia-inducible factor-1α (HIF-1α), a critical transcription factor associated with hypoxia, is also activated in disturbed flow by a mechanism that is independent of hypoxia. A final section of the review emphasizes hypoxia in vascular stenting that is used to enlarge vessels occluded by plaques. Stenting can compress the VV leading to hypoxia and associated intimal hyperplasia. To enhance oxygen transport during stenting, new stent designs with helical centrelines have been developed to increase blood phase oxygen transport rates and reduce intimal hyperplasia. Further study of the mechanisms controlling hypoxia in the artery wall may contribute to the development of therapeutic strategies for vascular diseases.

Although the coronary arteries are uniformly exposed to systemic cardiovascular risk factors, atherosclerosis development has a non-random distribution, which follows the local mechanical stresses including flow-related hemodynamic forces. Among these, wall shear stress plays an essential role and it represents the major flow-related factor affecting the distribution of atherosclerosis in coronary bifurcations. Furthermore, an emerging body of evidence suggests that hemodynamic factors such as low and oscillating wall shear stress may facilitate the development of in-stent restenosis and stent thrombosis after successful drug-eluting stent implantation. Drug-eluting stent implantation represents the gold standard for bifurcation interventions. In this specific setting of interventions on bifurcated lesions, the impact of fluid dynamics is expected to play a major role and constitutes substantial opportunity for future technical improvement. In the present review, available data is summarized regarding the role of local fluid dynamics in the clinical outcome of patients with bifurcated lesions.

Cells live in a complex and dynamic microenvironment, and a variety of microenvironmental cues can regulate cell behavior. In addition to biochemical signals, biophysical cues can induce not only immediate intracellular responses, but also long-term effects on phenotypic changes such as stem cell differentiation, immune cell activation and somatic cell reprogramming. Cells respond to mechanical stimuli via an outside-in and inside-out feedback loop, and the cell nucleus plays an important role in this process. The mechanical properties of the nucleus can directly or indirectly modulate mechanotransduction, and the physical coupling of the cell nucleus with the cytoskeleton can affect chromatin structure and regulate the epigenetic state, gene expression and cell function. In this review, we will highlight the recent progress in nuclear biomechanics and mechanobiology in the context of cell engineering, tissue remodeling and disease development.

Stem cells have shown great potential in vascular repair. Numerous evidence indicates that mechanical forces such as shear stress and cyclic strain can regulate the adhesion, proliferation, migration, and differentiation of stem cells via serious signaling pathways. The enrichment and differentiation of stem cells play an important role in the angiogenesis and maintenance of vascular homeostasis. In normal tissues, blood flow directly affects the microenvironment of vascular endothelial cells (ECs); in pathological status, the abnormal interactions between blood flow and vessels contribute to the injury of vessels. Next, the altered mechanical forces are transduced into cells by mechanosensors to trigger the reformation of vessels. This process occurs when signaling pathways related to EC differentiation are initiated. Hence, a deep understanding of the responses of stem cells to mechanical stresses and the underlying mechanisms involved in this process is essential for clinical translation. In this the review, we provide an overview of the role of stem cells in vascular repair, outline the performance of stem cells under the mechanical stress stimulation, and describe the related signaling pathways.

Flow diversion (FD) is a novel endovascular technique based on the profound alteration of cerebrovascular hemodynamics, which emerged as a promising minimally invasive therapy for intracranial aneurysms. However, delayed post-procedural stroke remains an unexplained concern. A consistent follow-up-regimen has not yet been defined, but is required urgently to clarify the underlying cause of delayed ischemia. In the last two years, 223 patients were treated with six different FD devices in our center. We identified subacute, FD-induced segmental vasospasm (SV) in 36 patients as a yet unknown, delayed-type reaction potentially compromising brain perfusion to a critical level. Furthermore, 86% of all patients revealed significant SV approximately four weeks after treatment. In addition, 56% had SV with 25% stenosis, and 80% had additional neointimal hyperplasia. Only 13% exhibited SV-related high-grade stenosis. One of those suffered stroke due to prolonged SV, requiring neurocritical care and repeated intra-arterial (i.a.) biochemical angioplasty for seven days to prevent territorial infarction. Five patients suffered newly manifested, transient hemicrania accompanying a compensatorily increased ipsilateral leptomeningeal perfusion. One treated vessel obliterated permanently. Hence, FD-induced SV is a frequent vascular reaction after FD treatment, potentially causing symptomatic ischemia or even stroke, approximately one month post procedure. A specifically early follow-up-strategy must be applied to identify patients at risk for ischemia, requiring intensified monitoring and potentially anti-vasospastic treatment.