Related Experiment Video
Updated: Oct 12, 2026
Transverse Aortic Constriction in Mice
Published on: April 21, 2010
ROCK1 plays an essential role in the transition from cardiac hypertrophy to failure in mice
Jianjian Shi1, Yi-Wei Zhang, Yu Yang
1Riley Heart Research Center, Wells Center for Pediatric Research, Indiana University, School of Medicine, Indianapolis, IN 46202-5225, USA.
Insights
Genetic deletion of Rho-associated coiled-coil containing protein kinase 1 (ROCK1) prevents heart failure progression in mice. ROCK1 deficiency protects against cardiac dilation, apoptosis, and improves survival in pathological cardiac hypertrophy.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Pathology
Background:
- Pathological cardiac hypertrophy can lead to heart failure.
- Rho-associated coiled-coil containing protein kinase 1 (ROCK1) plays a role in cardiac remodeling.
Purpose of the Study:
- To investigate if ROCK1 deficiency prevents the transition from cardiac hypertrophy to heart failure.
- To evaluate the therapeutic potential of targeting ROCK1 in heart failure.
Main Methods:
- Utilized transgenic mice with cardiac-restricted Gαq overexpression and ROCK1 knockout.
- Assessed cardiac function, apoptosis, and molecular markers in response to pregnancy stress and aging.
Main Results:
- ROCK1 deletion abolished peripartum mortality and attenuated cardiac dilation and dysfunction in Gαq mice.
- ROCK1 deficiency suppressed cardiomyocyte apoptosis, enhanced ERK/MAPK activation, and inhibited Bax translocation.
- ROCK1 deficiency improved survival and preserved cardiac function in aged Gαq mice.
Conclusions:
- ROCK1 deficiency confers long-term protection against hypertrophic decompensation and heart failure progression.
- ROCK1 is a potential therapeutic target for treating heart failure.
Abstract:
Pathological cardiac hypertrophy caused by diverse etiologies eventually leads to cardiac dilation and functional decompensation. We have recently reported that genetic deletion of Rho-associated coiled-coil containing protein kinase 1 (ROCK1) inhibited several pathological events including cardiomyocyte apoptosis in compensated hypertrophic hearts. The present study investigated whether ROCK1 deficiency can prevent the transition from hypertrophy to heart failure. Transgenic mice with cardiac-restricted overexpression of Gαq develop compensated cardiac hypertrophy at young ages, but progress into lethal cardiomyopathy accompanied by increased apoptosis after pregnancy or at old ages. The studies were first carried out using age- and pregnancy-matched wild-type, Gαq, ROCK1(-/-), and Gαq/ROCK1(-/-) mice. The potent beneficial effect of ROCK1 deletion is demonstrated by abolishment of peripartum mortality, and significant attenuation of left ventricular (LV) dilation, wall thinning, and contractile dysfunction in the peripartum Gαq transgenic mice. Increase in cardiomyocyte apoptosis was suppressed by ROCK1 deletion, associated with increased extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) activation and inhibition of mitochondrial translocation of Bax. In addition, ROCK1 deficiency also improved survival, inhibited cardiomyocyte apoptosis, and preserved LV dimension and function in old Gαq mice at 12 months. Furthermore, transgenic overexpression of ROCK1 increased cardiomyocyte apoptosis and accelerated hypertrophic decompensation in Gαq hearts in the absence of pregnancy stress. The present study provides for the first time in vivo evidence for the long-term beneficial effects of ROCK1 deficiency in hypertrophic decompensation and suggests that ROCK1 may be an attractive therapeutic target to limit heart failure progression.
