Learning from vascular remodelling.
The positioning of a hollow silicone collar around the carotid artery of a rabbit induces many changes of early atherosclerosis including intimal proliferation of smooth muscle cells. This occurs below an intact endothelium indicating that endothelial damage is not necessary for smooth muscle cell proliferation. The endothelium may in fact produce substances that control processes occurring in the intima. Vascular endothelial growth factor (VEGF) is an angiogenic agent that is produced by cultured vascular smooth muscle cells. The combination of hypoxia and factors such as platelet-derived growth factor, tumour necrosis factor alpha, basic fibroblast growth factor, and interleukin-1beta lead to synergistic production of VEGF by cultured smooth muscle cells. VEGF receptors are present predominantly on the endothelium and may be an important target for modulating the response to damage, hypoxia and inflammation. Transfection of the gene for VEGF resulted in inhibition or regression of intimal hyperplasia induced by the silicone collar in the rabbit. Studies suggest that the two mediators responsible for this inhibition of smooth muscle cell proliferation are nitric oxide and prostacyclin, which are produced by cultured endothelial cells incubated with VEGF. Thus, VEGF produced by smooth muscle cells in response to hypoxia, damage or inflammation, acts on specific endothelial receptors to produce nitric oxide and prostacyclin, which inhibit smooth muscle cell proliferation. Failure of this process could give rise to intimal hyperplasia. Early clinical studies of VEGF transfection from the outside of human arteries using a biodegradable collar are in progress.
Martin
J
J
Royal Free and University College Medical School, UK.
D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D016228:Endothelial Growth Factors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D008222:Lymphokines / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011817:Rabbits; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors