| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* The Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indiana University, School of Medicine, Indianapolis, Indiana, USA;
Section of Cardiovascular Sciences, Department of Medicine,
Center for Cardiovascular Development, Baylor College of Medicine, Houston, Texas, USA;
The Institute of Biosciences and Technology, The Texas A&M University System Health Science Center, Houston, Texas, USA
1Correspondence: The Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indiana University, School of Medicine, R4 building, Rm. 370, 1044 West Walnut St., Indianapolis, IN 46202-5225, USA. E-mail: lewei{at}iupui.edu
Ventricular myocyte hypertrophy is an important compensatory growth response to pressure overload. However, pathophysiological cardiac hypertrophy is accompanied by reactive fibrosis and remodeling. The Rho kinase family, consisting of ROCK1 and ROCK2, has been implicated in cardiac hypertrophy and ventricular remodeling. However, these previous studies relied heavily on pharmacological inhibitors, and not on gene deletion. Here we used ROCK1 knockout (ROCK1–/–) mice to investigate role of ROCK1 in the development of ventricular remodeling induced by transverse aortic banding. We observed that ROCK1 deletion did not impair compensatory hypertrophic response induced by pressure overload. However, ROCK1–/– mice exhibited reduced perivascular and interstitial fibrosis, which was observed at 3 wk but not at 1 wk after the banding. The reduced fibrosis in the myocardium of ROCK1–/– mice was closely associated with reduced expression of a variety of extracellular matrix (ECM) proteins and fibrogenic cytokines such as TGFß2 and connective tissue growth factor. This inhibitory effect of ROCK1 deletion on pathophysiological induction of fibrogenic cytokines was further confirmed in the myocardium of transgenic mice with cardiomyocyte-specific overexpression of G
q. Thus, these results indicate that ROCK1 contributes to the development of cardiac fibrosis and induction of fibrogenic cytokines in cardiomyocytes in response to pathological stimuli. Zhang, Y.-M., Bo, J., Taffet, G. E., Chang, J., Shi, J., Reddy, A. K., Michael, L. H., Schneider, M. D., Entman, M. L., Schwartz, R. J., Wei, L. Targeted deletion of ROCK1 protects the heart against pressure overload by inhibiting reactive fibrosis.
Key Words: Rho kinase • pressure overload • fibrosis • hypertrophy • fibrogenic cytokines
This article has been cited by other articles:
|
|
 |
|
  S. B. Haudek, D. Gupta, O. Dewald, R. J. Schwartz, L. Wei, J. Trial, and M. L. Entman Rho kinase-1 mediates cardiac fibrosis by regulating fibroblast precursor cell differentiation Cardiovasc Res, June 5, 2009; (2009) cvp135v3. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. H. Lee, J. Shi, N. H. Jeoung, M. S. Kim, J. M. Zabolotny, S. W. Lee, M. F. White, L. Wei, and Y.-B. Kim Targeted Disruption of ROCK1 Causes Insulin Resistance in Vivo J. Biol. Chem., May 1, 2009; 284(18): 11776 - 11780. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Zheng, Y. Chen, B. Pat, L. A. Dell'Italia, M. Tillson, A. R. Dillon, P. C. Powell, K. Shi, N. Shah, T. Denney, et al. Microarray Identifies Extensive Downregulation of Noncollagen Extracellular Matrix and Profibrotic Growth Factor Genes in Chronic Isolated Mitral Regurgitation in the Dog Circulation, April 21, 2009; 119(15): 2086 - 2095. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. P. Del Re, S. Miyamoto, and J. H. Brown Focal Adhesion Kinase as a RhoA-activable Signaling Scaffold Mediating Akt Activation and Cardiomyocyte Protection J. Biol. Chem., December 19, 2008; 283(51): 35622 - 35629. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Ohtsu, S. Higuchi, H. Shirai, K. Eguchi, H. Suzuki, A. Hinoki, E. Brailoiu, A. D. Eckhart, G. D. Frank, and S. Eguchi Central Role of Gq in the Hypertrophic Signal Transduction of Angiotensin II in Vascular Smooth Muscle Cells Endocrinology, July 1, 2008; 149(7): 3569 - 3575. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Phrommintikul, L. Tran, A. Kompa, B. Wang, A. Adrahtas, D. Cantwell, D. J. Kelly, and H. Krum Effects of a Rho kinase inhibitor on pressure overload induced cardiac hypertrophy and associated diastolic dysfunction Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1804 - H1814. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Kass, H. C. Champion, and J. A. Beavo Phosphodiesterase Type 5: Expanding Roles in Cardiovascular Regulation Circ. Res., November 26, 2007; 101(11): 1084 - 1095. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Goel, Y. Zhang, L. Anderson, and R. Rahimian Gender difference in rat aorta vasodilation after acute exposure to high glucose: Involvement of protein kinase C {beta} and superoxide but not of Rho Kinase Cardiovasc Res, November 1, 2007; 76(2): 351 - 360. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. L.M. Peters and M. C. Michel The RhoA/Rho kinase pathway in the myocardium Cardiovasc Res, July 1, 2007; 75(1): 3 - 4. [Full Text] [PDF]
|
|
|
|
|
|
L. Hauck, C. Harms, D. Grothe, J. An, K. Gertz, G. Kronenberg, R. Dietz, M. Endres, and R. von Harsdorf Critical Role for FoxO3a-Dependent Regulation of p21CIP1/WAF1 in Response to Statin Signaling in Cardiac Myocytes Circ. Res., January 5, 2007; 100(1): 50 - 60. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Yoneda, D. Ushakov, H. A.B. Multhaupt, and J. R. Couchman Fibronectin Matrix Assembly Requires Distinct Contributions from Rho Kinases I and -II Mol. Biol. Cell, January 1, 2007; 18(1): 66 - 75. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Fu, F. Liu, S. Su, W. Wang, X. R. Huang, M. L. Entman, R. J. Schwartz, L. Wei, and H. Y. Lan Signaling Mechanism of Renal Fibrosis in Unilateral Ureteral Obstructive Kidney Disease in ROCK1 Knockout Mice J. Am. Soc. Nephrol., November 1, 2006; 17(11): 3105 - 3114. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Chang, M. Xie, V. R. Shah, M. D. Schneider, M. L. Entman, L. Wei, and R. J. Schwartz Activation of Rho-associated coiled-coil protein kinase 1 (ROCK-1) by caspase-3 cleavage plays an essential role in cardiac myocyte apoptosis PNAS, September 26, 2006; 103(39): 14495 - 14500. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
