Plasma vascular endothelial growth factor and its receptor Flt-1 in patients with hyperlipidemia and atherosclerosis and the effects of fluvastatin or fenofibrate

Vitamins C and E downregulate vascular VEGF and VEGFR-2 expression in apolipoprotein-E-deficient mice

“…VEGF and VEGFR-2 expression were measured in apoE−/− mice, an accepted model of atherosclerosis showing high cholesterol concentration, increased lipid peroxidation [11] and low nitric oxide bioavailability [12]. We found higher levels of aorta and plasma VEGF in apoE−/− than in WT, in agreement with previous observations in the coronary arteries of hypercholesterolemic pigs [14], as well as in the plasma of hypercholesterolemic patients [13]. Moreover, increased vascular VEGF was accompanied by a marked upregulation in VEGFR-2 expression, a novel finding not described previously in hypercholesterolemia.…”

“…Although the pathophysiological meaning of the observed changes is not clear yet [13], given that systemic VEGF levels may not strictly reflect changes occurring in the vessel wall, its determination could become a valuable tool to investigate the relationship between hypercholesterolemia, atherosclerosis and angiogenesis, together with its pharmacological modulation.…”

“…Increased VEGF levels have been reported in plasma from hypercholesterolemic individuals [13] and in coronary arteries from hypercholesterolemic pigs [14]. Moreover, it has been shown that oxidized LDL, a key molecule in the atherosclerotic process, can upregulate VEGF expression in macrophages and endothelial cells, at least partially through the activation of PPAR␥ [15].…”

Spectrum of Pleiotropic Effects of Statins in Heart Failure

“…[27] VEGF levels in patients with hyperlipidemia are elevated, and have been shown in a small study to decrease after treatment with fluvastatin and fenofibrate. [28] Unfortunately the effects of fluvastatin vs fenofibrate vs simple lipid lowering could not be separated in this small clinical study because of the small sample size, but are nonetheless intriguing. [28] Treatment with statins has been shown to produce a biphasic effect on angiogenesis.…”

“…[28] Unfortunately the effects of fluvastatin vs fenofibrate vs simple lipid lowering could not be separated in this small clinical study because of the small sample size, but are nonetheless intriguing. [28] Treatment with statins has been shown to produce a biphasic effect on angiogenesis. Endothelial cells treated with low dose cerivastatin increased cell proliferation by 10-20%, while high concentrations decreased proliferation by 38%.…”