title: Plasma vascular endothelial growth factor and its receptor Flt-1 in patients with hyperlipidemia and atherosclerosis and the effects of fluvastatin or fenofibrate.
abstract: Increased vascular endothelial cell growth factor (VEGF) may be important in cardiovascular pathophysiology (perhaps relating to angiogenesis and collateral vessel development) and binds target endothelium via receptors such as Flt-1. We hypothesized that there would be increased levels of plasma VEGF and Flt-1 in patients with atherosclerosis and others with hyperlipidemia compared with controls, and a reduction in these factors with 3 months of lipid-lowering therapy. Twenty patients with uncomplicated hyperlipidemia but no atherosclerosis, 20 patients with hyperlipidemia plus clear atherosclerosis, and 40 matched controls were studied. Plasma VEGF was higher in patient groups than in healthy controls (p <0.01), but Flt-1 was not significantly altered. After lipid-lowering therapy, patients with uncomplicated hyperlipidemia had significantly reduced total cholesterol and VEGF (all p <0.05) but no significant change in Flt-1. Lack of a significant correlation between the von Willebrand factor and VEGF suggests the latter is unrelated to endothelial damage. Plasma VEGF that increases in patients with uncomplicated hyperlipidemia free of major underlying atherosclerosis and in patients with hyperlipidemia plus established atherosclerosis is reduced by successful lipid-lowering treatment. These findings may have implications for the pathophysiology and treatment of hyperlipidemia and atherosclerosis, and suggest an alternative mechanism (i.e., modulation of angiogenesis) by which lipid-lowering therapy may reduce cardiovascular events beyond lipid reduction alone.
authors.affiliation: Haemostasis, Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, United Kingdom. a.blann@bham.ac.uk
authors.forename: A D
authors.initials: AD
authors.lastname: Blann
authors.forename: F M
authors.initials: FM
authors.lastname: Belgore
authors.forename: J
authors.initials: J
authors.lastname: Constans
authors.forename: C
authors.initials: C
authors.lastname: Conri
authors.forename: G Y
authors.initials: GY
authors.lastname: Lip
mesh_terms: D000924:Anticholesteremic Agents / Q000627:therapeutic use; D001161:Arteriosclerosis / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D002784:Cholesterol / Q000097:blood; D016228:Endothelial Growth Factors / Q000097:blood*; D005229:Fatty Acids, Monounsaturated / Q000627:therapeutic use*; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use*; D000077340:Fluvastatin; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D007211:Indoles / Q000627:therapeutic use*; D008222:Lymphokines / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000097:blood*; D020794:Receptor Protein-Tyrosine Kinases / Q000097:blood*; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D042442:Vascular Endothelial Growth Factors; D014841:von Willebrand Factor / Q000032:analysis
chemical_list: D000924:Anticholesteremic Agents; D016228:Endothelial Growth Factors; D005229:Fatty Acids, Monounsaturated; D000960:Hypolipidemic Agents; D007211:Indoles; D008222:Lymphokines; D011518:Proto-Oncogene Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014841:von Willebrand Factor; D000077340:Fluvastatin; D002784:Cholesterol; D020794:Receptor Protein-Tyrosine Kinases; D040281:Vascular Endothelial Growth Factor Receptor-1; D011345:Fenofibrate