title: Stem cell antigen 1 protects against cardiac hypertrophy and fibrosis after pressure overload.
abstract: Stem cell antigen (Sca) 1, a glycosyl phosphatidylinositol-anchored protein localized to lipid rafts, is upregulated in the heart during myocardial infarction and renovascular hypertension-induced cardiac hypertrophy. It has been suggested that Sca-1 plays an important role in myocardial infarction. To investigate the role of Sca-1 in cardiac hypertrophy, we performed aortic banding in Sca-1 cardiac-specific transgenic mice, Sca-1 knockout mice, and their wild-type littermates. Cardiac hypertrophy was evaluated by echocardiographic, hemodynamic, pathological, and molecular analyses. Sca-1 expression was upregulated and detected in cardiomyocytes after aortic banding surgery in wild-type mice. Sca-1 transgenic mice exhibited significantly attenuated cardiac hypertrophy and fibrosis and preserved cardiac function compared with wild-type mice after 4 weeks of aortic banding. Conversely, Sca-1 knockout dramatically worsened cardiac hypertrophy, fibrosis, and dysfunction after pressure overload. Furthermore, aortic banding-induced activation of Src, mitogen-activated protein kinases, and Akt was blunted by Sca-1 overexpression and enhanced by Sca-1 deficiency. Our results suggest that Sca-1 protects against cardiac hypertrophy and fibrosis via regulation of multiple pathways in cardiomyocytes.
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Jiefang Rd 238, Wuhan 430060, People's Republic of China.
authors.forename: Heng
authors.initials: H
authors.lastname: Zhou
authors.forename: Zhou-Yan
authors.initials: ZY
authors.lastname: Bian
authors.forename: Jing
authors.initials: J
authors.lastname: Zong
authors.forename: Wei
authors.initials: W
authors.lastname: Deng
authors.forename: Ling
authors.initials: L
authors.lastname: Yan
authors.forename: Di-Fei
authors.initials: DF
authors.lastname: Shen
authors.forename: Haipeng
authors.initials: H
authors.lastname: Guo
authors.forename: Jia
authors.initials: J
authors.lastname: Dai
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: Ya-Fen
authors.initials: YF
authors.lastname: Lin
authors.forename: Xue
authors.initials: X
authors.lastname: Hu
authors.forename: Hongliang
authors.initials: H
authors.lastname: Li
authors.forename: Qi-Zhu
authors.initials: QZ
authors.lastname: Tang
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000502:physiology*; D006332:Cardiomegaly / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000517:prevention & control*; D004452:Echocardiography; D005355:Fibrosis / Q000503:physiopathology / Q000517:prevention & control; D006321:Heart / Q000503:physiopathology*; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D023421:Models, Animal; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D015854:Up-Regulation; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D000950:Antigens, Ly; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D019061:src-Family Kinases; D051057:Proto-Oncogene Proteins c-akt; D020929:Mitogen-Activated Protein Kinase Kinases