Endothelium in the control of vascular tone and growth: role of local mediators and mechanical forces.
Three major factors are involved in the development of atherosclerotic disease: 1) increased vasoconstrictor responses of the blood vessel wall; 2) increased platelet-vessel wall interaction and activation of coagulation factors; and 3) proliferative responses of vascular smooth muscle. Vascular smooth muscle cells proliferate in the media, migrate to the intima, and again proliferate on reaching the subendothelial space. In healthy blood vessels, these events do not occur due to the absence of growth promoters and/or the presence of growth inhibitors. Endothelial cells release growth inhibitors such as heparin sulphates and transforming growth factor beta 1 (TGF beta 1) as well as nitric oxide (NO) and prostacyclin. In rat vascular smooth muscle, NO inhibits proliferation and migration, particularly that induced by angiotensin II. Under certain conditions, the endothelium also releases growth promoters, such as basic fibroblast growth factor, platelet-derived growth factor (PDGF) and endothelin 1, which also can facilitate proliferative responses. Another important source of growth factors are adhering platelets which release PDGF and TGF beta 1 (albeit in its inactive form), and monocytes which are capable of releasing various growth factors. Furthermore, mechanical forces are important in the development of atherosclerosis, including transmural pressure and, in particular, pulsatile stretch. Indeed, heart rate is an independent risk factor for coronary artery disease and pulsatile stretch in vitro causes proliferation of human coronary as well as saphenous vein smooth muscle cells. The intracellular mediators involved in these proliferative responses are tyrosine kinase and S6 kinase. Calcium antagonists reduce only PDGF-induced proliferation whereas that due to mechanical forces is unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)
Lüscher
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Division of Cardiology, University Hospital, Inselspital Bern, Switzerland.
D000818:Animals; D001161:Arteriosclerosis / Q000473:pathology / Q000503:physiopathology; D001808:Blood Vessels / Q000254:growth & development*; D002455:Cell Division; D002465:Cell Movement; D001026:Coronary Artery Bypass; D004730:Endothelium, Vascular / Q000473:pathology / Q000502:physiology*; D006801:Humans; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D014666:Vasomotor System / Q000502:physiology*
D010982:Platelet-Derived Growth Factor