Vascular endothelial growth factor enhances atherosclerotic plaque progression.
Vascular endothelial growth factor (VEGF) can promote angiogenesis but may also exert certain effects to alter the rate of atherosclerotic plaque development. To evaluate this potential impact on plaque progression, we treated cholesterol-fed mice doubly deficient in apolipoprotein E/apolipoprotein B100 with low doses of VEGF (2 microg/kg) or albumin. VEGF significantly increased macrophage levels in bone marrow and peripheral blood and increased plaque area 5-, 14- and 4-fold compared with controls at weeks 1, 2 and 3, respectively. Plaque macrophage and endothelial cell content also increased disproportionately over controls. In order to confirm that the VEGF-mediated plaque progression was not species-specific, the experiment was repeated in cholesterol-fed rabbits at the three-week timepoint, which showed comparable increases in plaque progression.
Celletti
F L
FL
Cardiovascular and Interventional Radiology, Stanford University Medical Center, Stanford, California, USA.
Waugh
J M
JM
Amabile
P G
PG
Brendolan
A
A
Hilfiker
P R
PR
Dake
M D
MD
D000818:Animals; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000172:deficiency; D001057:Apolipoproteins E / Q000172:deficiency; D001161:Arteriosclerosis / Q000209:etiology* / Q000473:pathology; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D016228:Endothelial Growth Factors / Q000633:toxicity*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000473:pathology; D006801:Humans; D008222:Lymphokines / Q000633:toxicity*; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000473:pathology; D011817:Rabbits; D011994:Recombinant Proteins / Q000633:toxicity; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D001057:Apolipoproteins E; D016228:Endothelial Growth Factors; D008222:Lymphokines; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors