Amino acid and protein oxidation in cardiovascular disease.
Substantial evidence suggests that oxidative events contribute to the pathogenesis of atherosclerotic heart disease. For example, animal model data and numerous in vitro studies point to specific pathways as participants in disease initiation and progression. Moreover, recent clinical studies demonstrate clinical utility in monitoring systemic levels of protein-bound nitrotyrosine as a predictor of risk for coronary artery disease, atherosclerotic burden, and response to statin therapy. However, a definitive cause-and-effect relationship between oxidation and atherosclerosis has yet to be established, and multiple recent large prospective "antioxidant" intervention trials have failed to significantly impact upon disease risk and progression. In this review we highlight why such failures should not be taken as an indictment of the "Oxidation Hypothesis." Emphasis will be placed on discussion of molecular markers whose structures convey information about oxidation pathways leading to their formation, and which appear to be mechanistically linked to the disease process. Only through rational design of targeted interventions aimed at suppressing distinct oxidation pathways, with concomitant monitoring of antioxidant efficacy in human clinical studies, will answers to the role of oxidation in the pathogenesis of human atherosclerosis be defined.
Brennan
M-L
ML
Department of Cell Biology, Center for Cardiovascular Diagnostics and Prevention, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Hazen
S L
SL
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000201:enzymology / Q000378:metabolism*; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D010084:Oxidation-Reduction; D010586:Phagocytes / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D026361:Reactive Nitrogen Species / Q000378:metabolism; D014443:Tyrosine / Q000737:chemistry / Q000378:metabolism
D000596:Amino Acids; D005609:Free Radicals; D011506:Proteins; D026361:Reactive Nitrogen Species; D014443:Tyrosine