title: Smooth muscle phenotypic modulation: role in atherogenesis.
abstract: Observations in vivo and in vitro demonstrate: 1) smooth muscle cells are capable of more than one function and can alter their phenotype/state accordingly (modulation); 2) in the majority of cases before a smooth muscle can divide it must modulate from a contractile to a synthetic phenotype; 3) modulation is reversible; 4) however, if synthetic state smooth muscle which has been stimulated to divide achieves approximately nine cell doublings before being inhibited by confluence it appears unable to return to the contractile state; 5) smooth muscle cells in the synthetic state respond almost immediately to serum mitogens and have an altered ability to metabolize low density lipoprotein compared with those in the contractile state 6) diffuse intimal thickenings and intimal cushions at branch points form from the media apparently as a result of adaptation of the vessel wall to growth and development and are sites of predilection for the formation of atherosclerotic plaques. The "smooth muscle metabolic reactivity" hypothesis of atherogenesis suggests that due to the large number of smooth muscle cell doublings which occur in the formation of diffuse intimal thickenings and intimal cushions at branch points a number of these cells are permanently in the synthetic state. This confers upon these cells a selective proliferative advantage and an altered ability to metabolize lipoproteins - both essential ingredients in atherogenesis.
mesh_terms: D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology*; D002455:Cell Division; D002478:Cells, Cultured; D003238:Connective Tissue / Q000503:physiopathology; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D008934:Mitogens; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000503:physiopathology*; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000378:metabolism; D011973:Receptors, LDL
chemical_list: D008077:Lipoproteins, LDL; D008934:Mitogens; D011956:Receptors, Cell Surface; D011973:Receptors, LDL