Copyright ©The Author(s) 2015.
World J Diabetes. Jul 10, 2015; 6(7): 961-969
Published online Jul 10, 2015. doi: 10.4239/wjd.v6.i7.961
Table 1 Mechanisms of peripheral arterial disease in diabetes mellitus patients
Disease characteristicsMechanisms of pathologyDisease characteristics
DMHyperglycemiaVascular inflammationAtherosclerosisPAD
DyslipidemiaCRP: promotes leukocyte adhesion, coagulation, and chemotaxis; inhibits eNOS; impairs fibrinolysis(Increased plaque burden)
Insulin resistanceTNF-α and IL-6: activate NF-κβ, leading to thrombogenesis; promote leukocyte migration and adhesion, increasing plaque instability/ruptureAtherothrombosis (Increased plaque instability/rupture)
↑ FFA productionEndothelial cell dysfunctionRestenosis
Decreased NO production: inhibits vasodilation(Increased complexity)
Increased reactive oxygen species: inhibits vasodilation
Increased AGE production: is proinflammatory; induces leukocyte chemotaxis, adhesion, and transformation into foam cells
Vascular smooth muscle cell derangement
Tissue factor production: proatherogenic; procoagulation
FGF and TGF-α: Extracellular matrix production
Impaired synthesis of collagen: destabilizes plaque
Apoptosis of VSMC: increases risk of plaque rupture and thrombosis
Increased production of endothelin-1, angiotensin II, and prostanoids: leads to vasoconstriction
Platelet dysfunction
Enhanced uptake of glucose: increases oxidative stress; decreased NO production
Upregulation of P-selectin, GPIb, and GPIIb/IIIa receptors: promotes platelet adhesion and aggregation
Calcium dysregulation: increases platelet aggregation
Increased tissue factor and FVII production: enhances coagulability
Decreased antithrombin and protein C synthesis: enhances coagulability
Elevated blood viscosity
Increased fibrinogen production
Impaired arteriogenesis
Inhibited sensing of shear stress
Decreased monocyte and growth factor signaling