Characterizing the molecular landscape of venous congestion

Figure 4 Conceptual model of multisystem molecular dysregulation in venous congestion. Multiple pathobiologic mechanisms of venous congestion may be associated with the identified candidate circulating protein biomarkers. In venous congestion, elevated filling pressures in the heart may lead to myocardial stress (↑B-type natriuretic peptide, troponin, interleukin 1 receptor-like 1). This may contribute to endothelial dysfunction (↑endothelin 1, vascular endothelial growth factor, CD146, CA125, angiopoietin, vascular cell adhesion molecule 1), promoting vascular permeability and inflammation. Tissue edema (↑adiponectin, 7S domain of collagen type IV and hyaluronic acid) and systemic inflammatory processes (↑adrenomedullin, C-reactive protein, interleukin-6, tumor necrosis factor, fibroblast growth factor) may exacerbate organ dysfunction and, left unresolved, can lead to multiorgan failure involving the lungs, brain, liver, and kidneys (↑aspartate aminotransferase, alkaline phosphatase, gamma glutamyltransferase, Cystatin C, neutrophil gelatinase associated lipocalin, and hepatocyte growth factor). This interconnected network highlights the complex nature of venous congestion and its systemic effects that are yet to be investigated in critical illness. BNP: B-type natriuretic peptide; ST2: Interleukin 1 receptor-like 1; ET-1: Endothelin 1; VEGF: Vascular endothelial growth factor; CA125: Cancer antigen 125; ANGPT: Angiopoietin; VCAM: Vascular cell adhesion molecule 1; ADM: Adrenomedullin; CRP: C-reactive protein; IL-6: Interleukin-6; TNF: Tumor necrosis factor; FGF: Fibroblast growth factor; AST: Aspartate aminotransferase; ALP: Alkaline phosphatase; GGT: Gamma glutamyltransferase; NGAL: Neutrophil gelatinase associated lipocalin; HGF: Hepatocyte growth factor; P4NP7S: 7S domain of collagen type IV; HA: Hyaluronic acid.