Hypercholesterolemia promotes inflammation and microvascular dysfunction: role of nitric oxide and superoxide.
Relatively brief periods (days) of hypercholesterolemia can exert profound effects on endothelium-dependent functions of the microcirculation, including dilation of arterioles, fluid filtration across capillaries, and regulation of leukocyte recruitment in postcapillary venules. Hypercholesterolemia appears to convert the normal anti-inflammatory phenotype of the microcirculation to a proinflammatory phenotype. This phenotypic change appears to result from a decline in nitric oxide (NO) bioavailability that results from a reduction in NO biosynthesis, inactivation of NO by superoxide (O(2)(*)(-)), or both. A consequence of the hypercholesterolemia-induced microvascular responses is an enhanced vulnerability of the microcirculation to the deleterious effects of ischemia and other inflammatory conditions. Hence, therapeutic strategies that are directed towards preventing the early microcirculatory dysfunction and inflammation caused by hypercholesterolemia may prove effective in reducing the high mortality associated with ischemic tissue diseases. Agents that act to maintain the normal balance between NO and reactive oxygen species (ROS) in vascular endothelial cells may prove particularly useful in this regard.
Stokes
Karen Y
KY
Department of Molecular and Cellular Physiology, LSU Health Sciences Center, Shreveport, LA 71130-3932, USA.
Cooper
Dianne
D
Tailor
Anitaben
A
Granger
D Neil
DN
D000818:Animals; D001808:Blood Vessels / Q000473:pathology; D002318:Cardiovascular Diseases / Q000209:etiology / Q000378:metabolism; D002448:Cell Adhesion; D002791:Cholesterol, Dietary / Q000633:toxicity; D004730:Endothelium, Vascular / Q000473:pathology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D006937:Hypercholesterolemia / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D007249:Inflammation; D007511:Ischemia / Q000378:metabolism / Q000473:pathology; D007962:Leukocytes / Q000473:pathology; D008077:Lipoproteins, LDL / Q000378:metabolism; D008833:Microcirculation; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D010641:Phenotype; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014664:Vasodilation
D002791:Cholesterol, Dietary; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; D016328:NF-kappa B; D017382:Reactive Oxygen Species; C099252:oxidized low density lipoprotein; D013481:Superoxides; D009569:Nitric Oxide; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III