Importance of NAD(P)H Oxidase–Mediated Oxidative Stress and Contractile Type Smooth Muscle Myosin Heavy Chain SM2 at the Early Stage of Atherosclerosis
| Autor: | Mitsuyuki Hiromoto, Yoichi Toma, Masakazu Tanaka, Seiji Umemoto, Masunori Matsuzaki, Takashi Fujii, Shumpei Aoyagi, Yasuaki Tomochika, Shinichi Itoh |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Male
medicine.medical_specialty Vascular smooth muscle Nitric Oxide Synthase Type III Arteriosclerosis Hypercholesterolemia Probucol Aorta Thoracic medicine.disease_cause Antioxidants Muscle Smooth Vascular Superoxides Physiology (medical) Internal medicine Hyperlipidemia medicine Animals Protein Isoforms Myocyte NADH NADPH Oxidoreductases Pravastatin Myosin Heavy Chains biology business.industry Anticholesteremic Agents NADPH Dehydrogenase Membrane Transport Proteins NADPH Oxidases Smooth Muscle Myosins Phosphoproteins medicine.disease Actins Elasticity Disease Models Animal Oxidative Stress Cholesterol Endocrinology NAD(P)H oxidase biology.protein Diet Atherogenic Rabbits P22phox Nitric Oxide Synthase Cardiology and Cardiovascular Medicine business Oxidative stress medicine.drug |
| Zdroj: | Circulation. 105:2288-2295 |
| ISSN: | 1524-4539 0009-7322 |
| DOI: | 10.1161/01.cir.0000015607.33345.1f |
| Popis: | Background — Increased vascular oxidative stress induced by hyperlipidemia may alter the phenotype of vascular smooth muscle (SM) cells and play a crucial role in the progression of atherosclerosis. To clarify the mechanisms underlying vascular dysfunction and oxidative stress in hypercholesterolemia, we compared the effects of antioxidant probucol with those of pravastatin on aortic stiffness, phenotypic modulation, oxidative stress, and NAD(P)H oxidase essential subunit p22 phox expression in aortic medial SM cells of cholesterol-fed rabbits by using color image analysis of immunostained sections. Methods and Results — Japanese white male rabbits were fed either normal chow or 1% cholesterol diet for 14 weeks. After the first 7 weeks, cholesterol-fed rabbits were further divided into 3 groups: those fed with cholesterol feed only and those additionally given pravastatin (10 mg/d) or probucol (1.3 g/d) for the last 7 weeks. Within 7 weeks of treatment, probucol improved aortic stiffness more effectively than did pravastatin, inhibiting phenotypic modulation by selectively upregulating contractile-type SM myosin heavy chain isoform SM2 and by reducing both p22 phox and superoxide content in medial SM cells of cholesterol-fed rabbit aorta. No significant differences in cholesterol levels, superoxide content, and endothelial NO synthase levels in the intima, aortic morphology and fibrosis, and synthetic-type myosin heavy chain in medial SM cells were observed between the 2 drug-treated groups. Conclusions — These results suggest that oxidative stress and SM2 in medial SM cells might be important factors for vascular dysfunction, and strategies aimed at blocking NAD(P)H oxidase and upregulating SM2 may have therapeutic potential against the progression of atherosclerosis in hypercholesterolemia. |
| Databáze: | OpenAIRE |
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