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 underlyi ng mechanisms for these deleterious effects involve a local inflammatory re sponse and release of cytokines and growth factors. Consequent activation o f oxidation-sensitive mechanisms in the arterial wall, modulation of intrac ellular signaling pathways, increased oxidation of low-density lipoprotein cholesterol, and quenching of nitric oxide can all impair the functions con trolled by the vascular wall and lead to the development of atherosclerosis , This cascade represents a common pathological mechanism activated by vari ous cardiovascular risk factors and may partly underlie synergism among the m as well as the early pathogenesis of atherosclerosis, Antioxidant interve ntion and restoration of the bioavailability of nitric oxide have been show n to mitigate functional and structural arterial alterations and improve ca rdiovascular outcomes. Elucidation of the precise nature and role of early transductional signaling pathways and transcriptional events activated in h ypercholesterolemia in children and adults, including mothers during pregna ncy, and understanding their downstream effects responsible for atherogenes is may help in directing preventive and interventional measures against ath erogenesis and vascular dysfunction.