Influence of caveolin, cholesterol, and lipoproteins on nitric oxide synthase: implications for vascular disease.
Caveolin-1 traffics cholesterol between the endoplasmic reticulum and cell surface caveolae in a non-vesicle chaperone complex which contains heat shock protein 56, cyclophilin 40, and cyclophilin A. Recent studies demonstrate that endothelial nitric oxide synthase (eNOS), caveolin, hetero-trimeric G-protein coupled receptors, and a calcium channel form an activation complex that is associated with cholesterol-rich caveolae. Oxidized LDL depletes caveolae of cholesterol and prevents agonist stimulation of eNOS by disrupting the activation complex. HDL antagonizes the effects of oxLDL by donating cholesterol to caveolae, thereby preserving the structure and function of caveolae. These findings and others provide a possible mechanistic basis for some of the molecular changes observed in vascular disease.
Everson
W V
WV
Department of Physiology, University of Kentucky, Lexington, KY 40536, USA.
Smart
E J
EJ
D051242:Caveolin 1; D022461:Caveolins / Q000494:pharmacology*; D002784:Cholesterol / Q000494:pharmacology*; D006801:Humans; D008074:Lipoproteins / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D018110:Receptors, Lipoprotein / Q000378:metabolism; D014652:Vascular Diseases / Q000378:metabolism*
C495540:CAV1 protein, human; D051242:Caveolin 1; D022461:Caveolins; D008074:Lipoproteins; D018110:Receptors, Lipoprotein; D002784:Cholesterol; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III