Hyperlipidemia induces vascular smooth muscle cell proliferation involving Wnt/β-catenin signaling.
Hyperlipidemia has been shown to stimulate vascular smooth muscle cell (VSMC) proliferation. Wnt signaling pathway plays a critical role in embryonic development and cell proliferation. In this study, Sprague-Dawley rats fed with high-fat or normal diet for 12 weeks were sacrificed, and the thoracic aorta was harvested to determine wnt3a, β-catenin, T-cell factor 4 (TCF4), and cyclin D1 expressions. VSMC proliferation within thoracic aorta and lipid accumulation within VSMCs were detected. Rat aortic VSMCs were cultured in serum from rats with hyperlipidemia or DKK-1; Wnt3a, β-catenin, TCF4, and cyclin D1 expressions, and cell cycle distribution were determined. The findings demonstrated that increased number of VSMCs, lipid droplets, and vacuoles within thoracic aorta in the high-fat-fed group. Compared with controls, VSMCs from high-fat-fed rats showed higher mRNA expressions of wnt3a, β-catenin, TCF4, and cyclin D1, as well as in VSMCs cultured with hyperlipidemic serum. After 24 h, VSMCs stimulated with hyperlipidemic serum showed significantly increased cell number and S-phase entry compared with cells exposed to normolipidemic serum. These effects were blocked by DKK-1. These results suggest that Wnt/β-catenin signaling plays an important role in hyperlipidemia-induced VSMC proliferation.
Department of Cardiovascular Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai, 200080, PR China.
Yu
Y
Zhuang
Department of Cardiovascular Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai, 200080, PR China.
Jian-Qiang
JQ
Mao
Department of Cardiovascular Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai, 200080, PR China.
Min
M
Yu
Department of Cardiovascular Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai, 200080, PR China.
Li-Ya
LY
Dong
Department of Cardiovascular Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai, 200080, PR China.
Yong-Liang
YL
Fan
Department of Cardiothoracic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, 200233, PR China.
Zhi-Qian
ZQ
Lv
Department of Cardiovascular Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai, 200080, PR China.
Ming-Di
MD
Xiao
Department of Cardiovascular Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai, 200080, PR China.
Zhong-Xiang
ZX
Yuan
D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D059305:Diet, High-Fat; D006949:Hyperlipidemias / Q000378:metabolism* / Q000473:pathology*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
C531384:Dkk1 protein, rat; D036341:Intercellular Signaling Peptides and Proteins; D051176:beta Catenin
Wnt signaling pathway; hyperlipidemia; proliferation; vascular smooth muscle cells; β-catenin