title: Manganese superoxide dismutase inhibits neointima formation through attenuation of migration and proliferation of vascular smooth muscle cells.
abstract: Superoxide anion is elevated during neointima development and is essential for neointimal vascular smooth muscle cell (VSMC) proliferation. However, little is known about the role of manganese superoxide dismutase (MnSOD, SOD2) in the neointima formation following vascular injury. SOD2 in the mitochondria plays an important role in cellular defense against oxidative damage. Because of its subcellular localization, SOD2 is considered the first line of defense against oxidative stress and plays a central role in metabolizing superoxide. Because mitochondria are the most important sources of superoxide anion, we speculated that SOD2 may have therapeutic benefits in preventing vascular remodeling. In this study, we used a rat carotid artery balloon-injury model and an adenoviral gene delivery approach to test the hypothesis that SOD2 suppresses vascular lesion formation. SOD2 was activated along with the progression of neointima formation in balloon-injured rat carotid arteries. Depletion of SOD2 by RNA interference markedly promoted the lesion formation, whereas SOD2 overexpression suppressed the injury-induced neointima formation via attenuation of migration and proliferation of VSMCs. SOD2 exerts its inhibitory effect on VSMC migration induced by angiotensin II by scavenging superoxide anion and suppressing the phosphorylation of Akt. Our data indicate that SOD2 is a negative modulator of vascular lesion formation after injury. Therefore, SOD2 augmentation may be a promising therapeutic strategy for the prevention of lesion formation in proliferative vascular diseases such as restenosis.
authors: Department of Physiology & Pharmacology, University of Georgia, Athens, GA 30602, USA.
authors: Jia-Ning
authors: JN
authors: Wang
authors: Ning
authors: N
authors: Shi
authors: Shi-You
authors: SY
authors: Chen
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000804:Angiotensin II / Q000008:administration & dosage; D000818:Animals; D002339:Carotid Arteries / Q000201:enzymology* / Q000473:pathology; D020212:Carotid Artery Injuries / Q000201:enzymology* / Q000209:etiology / Q000235:genetics / Q000517:prevention & control; D002404:Catheterization / Q000009:adverse effects; D002465:Cell Movement; D049109:Cell Proliferation; D023903:Coronary Restenosis / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control; D018014:Gene Transfer Techniques; D008297:Male; D008928:Mitochondria / Q000201:enzymology* / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000201:enzymology* / Q000473:pathology; D058426:Neointima / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D013481:Superoxides / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D013481:Superoxides; D000804:Angiotensin II; D013482:Superoxide Dismutase; D051057:Proto-Oncogene Proteins c-akt