Vascular endothelial growth factor and its receptor, Flt-1, in the plasma of patients with coronary or peripheral atherosclerosis, or Type II diabetes

Abstract

Since atherosclerosis is characterized by endothelial damage, re-growth seems likely to be occurring in order to repair or replace injured cells. Angiogenic vascular endothelial growth factor (VEGF), a likely mediator of these events, acts on the endothelium via a specific receptor, Flt-1. We hypothesized that patients with different manifestations of atherosclerosis, and others with diabetes, would have altered plasma levels of VEGF and Flt-1 compared with healthy individuals. Accordingly, 70 patients with peripheral artery disease (PAD), 70 patients with coronary artery disease (CAD), and 70 age- and sex-matched healthy controls were recruited. We also recruited 14 patients with diabetes asymptomatic for atherosclerosis, 14 patients with diabetes and atherosclerosis, and 14 age- and sex-matched controls. VEGF and soluble Flt-1 (sFlt-1) were measured by ELISA. In the main study of PAD and CAD, VEGF was raised in both patient groups (P<0.05) compared with the controls, but was not different between the patient groups. sFlt-1 was lower in patients with PAD (P<0.05), but not in those with CAD, compared with the controls. VEGF was raised in the patients with diabetes plus atherosclerosis (P<0.05), but not in the group with diabetes alone; levels of sFlt-1 were unaltered in both diabetes groups. Our data point to changes in plasma levels of VEGF and its receptor sFlt-1 in diabetes and atherosclerosis that may have relevance for therapy and angiogenesis in these conditions.

Resveratrol ameliorates high-glucose-induced hyperpermeability mediated by caveolae via VEGF/KDR pathway

“…As the inter-endothelial junction discontinuities are less than 3 nm and can only account for the passage of small molecules (Michel and Curry 1999), it was generally considered that macromolecules pass through the endothelium in transcellular way, most likely to be mediated by caveolae. Elevated plasma VEGF was observed in both diabetic patients with atherosclerosis and diabetic model of rabbit (Blann et al 2002;Laakso 2008). In vitro studies demonstrated that high glucose induced VEGF in mesangial cells, glomerular podocytes, and retinal pigmented epithelial cells (Senger et al 1990;Hoshi et al 2002;Sone et al 1996).…”

Influence of diabetes on endothelial cell response during sepsis

“…Similarly, high concentrations of PAI-1 and subsequent downregulation of fibrinolysis have been implicated in the increasing morbidity, mortality and risks for thrombotic disease in diabetic patients [18,19]. VEGF and sFLT-1 may also play a role in the pathophysiology of atherosclerosis by initiating and propagating angiogenesis, and thereby providing a passage for inflammatory cells to the site of injury [29]. Increased concentrations of VEGF and sFLT-1 have been reported in patients with diabetes, and they may play a role in the development of diabetic nephropathy and retinopathy [20].…”

Impact of type 2 diabetes on the plasma levels of vascular endothelial growth factor and its soluble receptors type 1 and type 2 in patients with peripheral arterial disease

“…Date are expressed as mean±standard deviation (SD). The difference is considered to be significant at P-value of <0.05 (in bold) Blann et al (2002) assessed the expression of angiogenic factors in plasma of patients with type 2 diabetes, and revealed significantly higher VEGF concentrations in diabetic patients comparable with healthy subjects. Similarly higher VEGF concentrations in plasma of patients with PAD irrespective of diabetes (non-)coexistence were reported by Botti et al (2012).…”