Involvement of oxidation-sensitive mechanisms in the cardiovascular effects of hypercholesterolemia.
Hypercholesterolemia is a common clinical metabolic and/or genetic disorder that promotes functional and structural vascular wall injury. The underlying mechanisms for these deleterious effects involve a local inflammatory response and release of cytokines and growth factors. Consequent activation of oxidation-sensitive mechanisms in the arterial wall, modulation of intracellular signaling pathways, increased oxidation of low-density lipoprotein cholesterol, and quenching of nitric oxide can all impair the functions controlled by the vascular wall and lead to the development of atherosclerosis. This cascade represents a common pathological mechanism activated by various cardiovascular risk factors and may partly underlie synergism among them as well as the early pathogenesis of atherosclerosis. Antioxidant intervention and restoration of the bioavailability of nitric oxide have been shown to mitigate functional and structural arterial alterations and improve cardiovascular outcomes. Elucidation of the precise nature and role of early transductional signaling pathways and transcriptional events activated in hypercholesterolemia in children and adults, including mothers during pregnancy, and understanding their downstream effects responsible for atherogenesis may help in directing preventive and interventional measures against atherogenesis and vascular dysfunction.
Napoli
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C
Department of Medicine, University of Naples, Italy. claunap@tin.it
Lerman
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LO
D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D001161:Arteriosclerosis / Q000209:etiology* / Q000517:prevention & control; D001682:Biological Availability; D016207:Cytokines / Q000502:physiology; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism*; D006133:Growth Substances / Q000502:physiology; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications* / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000517:prevention & control; D007249:Inflammation; D009569:Nitric Oxide / Q000502:physiology; D010084:Oxidation-Reduction; D017410:Practice Guidelines as Topic; D011379:Prognosis; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012307:Risk Factors; D016896:Treatment Outcome
D000975:Antioxidants; D016207:Cytokines; D006133:Growth Substances; D017382:Reactive Oxygen Species; D009569:Nitric Oxide