Soluble VEGF receptor sFlt-1, angiogenesis and heart failure

Microvascular remodeling has been extensively recognized in the myocardium of patients with CKD and uremic animals. Diminished capillary density is not restricted to the hearts, since the skin of dialysis patients, as well as the kidneys and hind-limbs of animal models of CKD are also affected. Thus CKD is noted as a state of anti-angiogenesis, which could be explained by the accumulation of factors that negatively affect endothelial function, including angiogenic competence.

One of these anti-angiogenic factors is the soluble form of the vascular endothelial growth factor (VEGF) receptor 1, also called sFlt-1. We have shown that sFlt-1 induces endothelial cell apoptosis and impairs angiogenesis in vitro. In patients, sFlt-1 increases when renal function decreases, and correlates positively not only with markers of endothelial dysfunction, but also with the Framingham risk score and cardiovascular events (stroke and myocardial infarction). Our findings suggest that sFlt-1 contributes to endothelial dysfunction, and might serve as a diagnostic marker in CKD patients at high CVD risk (JASN, 2009).

Further studies have focused on the role of sFlt-1 on heart failure, as well as on the regulatory mechanisms involved in increased sFlt-1 production in renal disease.