Published Online
on November 8, 2004

A more recent version of this article appeared on December 1, 2004

This Article Full Text (PDF) All Versions of this Article: 44/6/826    most recent 01.HYP.0000148458.03202.48v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Xie, Z. Articles by Singh, K. Search for Related Content PubMed PubMed Citation Articles by Xie, Z. Articles by Singh, K. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Substance via MeSH Related Collections Remodeling Hypertrophy

Submitted on August 26, 2004
Revised on September 7, 2004

Osteopontin Modulates Myocardial Hypertrophy in Response to Chronic Pressure Overload in Mice

Zhonglin Xie; Mahipal Singh; and Krishna Singh^*

From the Department of Physiology, James H. Quillen College of Medicine, James H. Quillen Veterans Affairs Medical Center, East Tennessee State University, Johnson City, Tenn.

^* To whom correspondence should be addressed. E-mail: singhk{at}mail.etsu.edu.

Abstract--Osteopontin (OPN) expression increases in the heart during hypertrophy and heart failure. Here, we studied the role of OPN in pressure overload-induced hypertrophy and analyzed the signaling pathways involved in hypertrophy. Aortic banding (AB) was performed in a group of wild-type (WT) and OPN knockout (KO) mice to induce pressure overload. Left ventricular (LV) structural and functional remodeling was studied 1 month after AB. AB increased OPN and 1 integrin (a receptor for OPN) protein expression in WT-AB group. Hypertrophic response as measured by increased heart weight-to-body weight ratio and myocyte cross-sectional area was significantly increased in WT-AB and KO-AB groups when compared with their respective shams. However, the increase was significantly higher in WT-AB. Re-expression of atrial natriuretic factor was only detected in WT-AB group. LV end-diastolic pressure-volume curve obtained using Langendorff perfusion analysis exhibited a leftward shift in WT-AB group, not in KO-AB. LV-developed pressures measured over a range of LV volumes were significantly increased in WT-AB, not in KO-AB mice. Increased phosphorylation of c-Jun N-terminal kinases, p38 kinase, Akt, and glycogen synthase kinase-3 was significantly higher in WT-AB when compared with KO-AB group. Increased OPN expression may play an essential role in modulating compensatory cardiac hypertrophy in response to chronic pressure overload.

Key words: heart • hypertrophy • kinase

This article has been cited by other articles:

				S. M. Swift, B. R. Gaume, K. M. Small, B. J. Aronow, and S. B. Liggett Differential coupling of Arg- and Gly389 polymorphic forms of the {beta}1-adrenergic receptor leads to pathogenic cardiac gene regulatory programs Physiol Genomics, September 17, 2008; 35(1): 123 - 131. [Abstract] [Full Text] [PDF]

				M. Rosenberg, C. Zugck, M. Nelles, C. Juenger, D. Frank, A. Remppis, E. Giannitsis, H. A. Katus, and N. Frey Osteopontin, a New Prognostic Biomarker in Patients With Chronic Heart Failure Circ Heart Fail, May 1, 2008; 1(1): 43 - 49. [Abstract] [Full Text] [PDF]

				F. G. Spinale Myocardial Matrix Remodeling and the Matrix Metalloproteinases: Influence on Cardiac Form and Function Physiol Rev, October 1, 2007; 87(4): 1285 - 1342. [Abstract] [Full Text] [PDF]

				T. Oka, J. Xu, R. A. Kaiser, J. Melendez, M. Hambleton, M. A. Sargent, A. Lorts, E. W. Brunskill, G. W. Dorn II, S. J. Conway, et al. Genetic Manipulation of Periostin Expression Reveals a Role in Cardiac Hypertrophy and Ventricular Remodeling Circ. Res., August 3, 2007; 101(3): 313 - 321. [Abstract] [Full Text] [PDF]

				V. Subramanian, P. Krishnamurthy, K. Singh, and M. Singh Lack of osteopontin improves cardiac function in streptozotocin-induced diabetic mice Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H673 - H683. [Abstract] [Full Text] [PDF]

				P. A. Arias-Loza, K. Hu, A. Schafer, J. Bauersachs, T. Quaschning, J. Galle, V. Jazbutyte, L. Neyses, G. Ertl, K.-H. Fritzemeier, et al. Medroxyprogesterone Acetate But Not Drospirenone Ablates the Protective Function of 17{beta}-Estradiol in Aldosterone Salt-Treated Rats Hypertension, November 1, 2006; 48(5): 994 - 1001. [Abstract] [Full Text] [PDF]

				K. C. Bilchick, S. K. Saha, E. Mikolajczyk, L. Cope, W. J. Ferguson, W. Yu, S. Girouard, and D. A. Kass Differential regional gene expression from cardiac dyssynchrony induced by chronic right ventricular free wall pacing in the mouse Physiol Genomics, September 14, 2006; 26(2): 109 - 115. [Abstract] [Full Text] [PDF]

				A. M. Deschamps and F. G. Spinale Pathways of matrix metalloproteinase induction in heart failure: Bioactive molecules and transcriptional regulation Cardiovasc Res, February 15, 2006; 69(3): 666 - 676. [Abstract] [Full Text] [PDF]

				K. Graf and P. Stawowy Osteopontin: A Protective Mediator of Cardiac Fibrosis? Hypertension, December 1, 2004; 44(6): 809 - 810. [Full Text] [PDF]