title: Regulator of G protein signaling 5 protects against cardiac hypertrophy and fibrosis during biomechanical stress of pressure overload.
abstract: The development of cardiac hypertrophy in response to increased hemodynamic load and neurohormonal stress is initially a compensatory response that may eventually lead to ventricular dilation and heart failure. Regulator of G protein signaling 5 (Rgs5) is a negative regulator of G protein-mediated signaling by inactivating Galphaq and Galphai, which mediate actions of most known vasoconstrictors. Previous studies have demonstrated that Rgs5 expresses among various cell types within mature heart and showed high levels of Rgs5 mRNA in monkey and human heart tissue by Northern blot analysis. However, the critical role of Rgs5 on cardiac remodeling remains unclear. To specifically determine the role of Rgs5 in pathological cardiac remodeling, we used transgenic mice with cardiac-specific overexpression of human Rgs5 gene and Rgs5-/- mice. Our results demonstrated that the transgenic mice were resistant to cardiac hypertrophy and fibrosis through inhibition of MEK-ERK1/2 signaling, whereas the Rgs5-/- mice displayed the opposite phenotype in response to pressure overload. These studies indicate that Rgs5 protein is a crucial component of the signaling pathway involved in cardiac remodeling and heart failure.
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China. lihl@whu.edu.cn
authors.forename: Hongliang
authors.initials: H
authors.lastname: Li
authors.forename: Chengwei
authors.initials: C
authors.lastname: He
authors.forename: Jinhua
authors.initials: J
authors.lastname: Feng
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Qizhu
authors.initials: Q
authors.lastname: Tang
authors.forename: Zhouyan
authors.initials: Z
authors.lastname: Bian
authors.forename: Xue
authors.initials: X
authors.lastname: Bai
authors.forename: Heng
authors.initials: H
authors.lastname: Zhou
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.forename: Scott P
authors.initials: SP
authors.lastname: Heximer
authors.forename: Mu
authors.initials: M
authors.lastname: Qin
authors.forename: He
authors.initials: H
authors.lastname: Huang
authors.forename: Peter P
authors.initials: PP
authors.lastname: Liu
authors.forename: Congxin
authors.initials: C
authors.lastname: Huang
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism* / Q000473:pathology*; D002478:Cells, Cultured; D005355:Fibrosis / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051379:Mice; D018345:Mice, Knockout; D009928:Organ Specificity; D011312:Pressure; D020710:RGS Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D013314:Stress, Mechanical; D013312:Stress, Physiological
chemical_list: D020710:RGS Proteins; C491349:RGS5 protein, human; C105346:Rgs5 protein, mouse