Overexpression of Mitofusin 2 inhibited oxidized low-density lipoprotein induced vascular smooth muscle cell proliferation and reduced atherosclerotic lesion formation in rabbit.
Our previous studies have implies that Mitofusin 2 (Mfn2), which was progressively reduced in arteries from ApoE(-/-) mice during the development of atherosclerosis, may take part in pathogenesis of atherosclerosis. In this study, we found that overexpression of Mfn2 inhibited oxidized low-density lipoprotein or serum induced vascular smooth muscle cell proliferation by down-regulation of Akt and ERK phosphorylation. Then we investigated the in vivo role of Mfn2 on the development of atherosclerosis in rabbits using adenovirus expressing Mitofusin 2 gene (AdMfn2). By morphometric analysis we found overexpression of Mfn2 inhibited atherosclerotic lesion formation and intima/media ratio by 66.7% and 74.6%, respectively, compared with control group. These results suggest that local Mfn2 treatment suppresses the development of atherosclerosis in vivo in part by attenuating the smooth muscle cell proliferation induced by lipid deposition and vascular injury.
Guo
Yan-Hong
YH
Department of Cardiology, Peking University Third Hospital, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, No. 49, North Garden Road, Beijing 100083, China.
Chen
Kuanghueih
K
Gao
Wei
W
Li
Qian
Q
Chen
Li
L
Wang
Gui-Song
GS
Tang
Jian
J
D000818:Animals; D002340:Carotid Artery Diseases / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D049109:Cell Proliferation; D002478:Cells, Cultured; D020558:GTP Phosphohydrolases; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism; D010084:Oxidation-Reduction; D011817:Rabbits; D015854:Up-Regulation
D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D020558:GTP Phosphohydrolases; C470018:MFN2 protein, human