Possibility of the regression of atherosclerosis through the prevention of endothelial senescence by the regulation of nitric oxide and free radical scavengers.
In the elderly, atherosclerotic diseases such as stroke and myocardial infarction occupy a major part of their causes of death and care. The elderly always have atherosclerosis in their aorta and other arteries and are exposed to risk of attacks. It is the elderly who should receive its safe, harmless and advanced treatment. Advanced stage of atherosclerosis in the elderly is progressed by complicated risk factors such as dyslipidemia and diabetes mellitus and specific risk factors for the elderly, aging (and menopause). Treatment of atherosclerotic disease may need special ones targeted for the elderly. Recent studies reported that frequencies of dyslipidemia were not decreased in the older oldest. In the elderly, impaired glucose tolerance occurs and it progresses atherosclerosis. Endothelial dysfunction like impairment of nitric oxide (NO) bioavailability also progresses atherosclerosis. Although we tried to regress the high cholesterol diet-induced atherosclerosis in rabbit aorta with a normal diet with or without statin, regression could not be achieved. NO targeting gene therapy (adenovirus endothelial nitric oxide synthase [eNOS] gene vector) regressed 20% of atherosclerotic lesions through reduction of lipid contents, however, a more integrated strategy is important for complete regression. We paid attention to NO bioavailability and developed two ways of increasing it in atherosclerosis: citrulline therapy and arginase II inhibition by estrogen. Further, we found a close relation between atherosclerosis and endothelial senescence and that NO can prevent it, especially in a diabetic model. Taken together, regression of atherosclerosis can be achieved by not only regulation of various risk factors but regulation of the cross-talk of NO and free radicals.
Hayashi
Toshio
T
Department of Geriatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan. hayashi@med.nagoya-u.ac.jp
Iguchi
Akihisa
A
D000368:Aged; D000375:Aging / Q000502:physiology*; D000818:Animals; D002340:Carotid Artery Diseases / Q000188:drug therapy / Q000503:physiopathology*; D002478:Cells, Cultured; D003925:Diabetic Angiopathies / Q000503:physiopathology / Q000517:prevention & control; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000502:physiology; D004967:Estrogens / Q000502:physiology; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*
D004967:Estrogens; D017382:Reactive Oxygen Species; D009569:Nitric Oxide