Regulator of G protein signaling 5 protects against cardiac hypertrophy and fibrosis during biomechanical stress of pressure overload.
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.
Li
Hongliang
H
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China. lihl@whu.edu.cn
He
Chengwei
C
Feng
Jinhua
J
Zhang
Yan
Y
Tang
Qizhu
Q
Bian
Zhouyan
Z
Bai
Xue
X
Zhou
Heng
H
Jiang
Hong
H
Heximer
Scott P
SP
Qin
Mu
M
Huang
He
H
Liu
Peter P
PP
Huang
Congxin
C
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
D020710:RGS Proteins; C491349:RGS5 protein, human; C105346:Rgs5 protein, mouse