(Hypertension. 1999;33:663-670.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
Myocardial Osteopontin Expression Coincides With the Development of Heart Failure
From the Myocardial Biology Unit and Cardiovascular Division, Department of Medicine, Boston Medical Center, Boston Veterans Affairs Medical Center and Boston University School of Medicine, Boston, Mass.
Correspondence to Krishna Singh, PhD, Myocardial Biology Unit, Boston University School of Medicine, 80 E Concord St, Boston, MA 02118. E-mail krishna.singh{at}bmc.org
Abstract—To identify genes that
are differentially expressed during the transition from compensated
hypertrophy to failure, myocardial mRNA from spontaneously
hypertensive rats (SHR) with heart failure (SHR-F) was compared with
that from age-matched SHR with compensated hypertrophy
(SHR-NF) and normotensive Wistar-Kyoto rats (WKY) by differential
display reverse transcriptase–polymerase chain reaction.
Characterization of a transcript differentially expressed in SHR-F
yielded a cDNA with homology to the extracellular matrix protein
osteopontin. Northern analysis showed low levels of osteopontin
mRNA in left ventricular myocardium from WKY
and SHR-NF but a markedly increased (
10-fold) level in SHR-F. In
myocardium from WKY and SHR-NF, in situ hybridization
showed only scant osteopontin mRNA, primarily in arteriolar cells. In
SHR-F, in situ hybridization revealed abundant expression of
osteopontin mRNA, primarily in nonmyocytes in the
interstitial and perivascular space. Similar findings for
osteopontin protein were observed in the midwall region of
myocardium from the SHR-F group. Consistent with
the findings in SHR, osteopontin mRNA was minimally increased
(1.9-fold) in left ventricular myocardium
from nonfailing aortic-banded rats with pressure-overload
hypertrophy but was markedly increased (8-fold) in
banded rats with failure. Treatment with captopril starting before or
after the onset of failure in the SHR reduced the increase in left
ventricular osteopontin mRNA levels. Thus, osteopontin
expression is markedly increased in the heart coincident with the
development of heart failure. The source of osteopontin in SHR-F is
primarily nonmyocytes, and its induction is inhibited by an
angiotensin-converting enzyme inhibitor,
suggesting a role for angiotensin II. Given the known
biological activities of osteopontin, including cell adhesion and
regulation of inducible nitric oxide synthase gene expression, these
data suggest that it could play a role in the pathophysiology of
heart failure.
Key Words: osteopontin • heart • heart failure • rats, inbred SHR • hypertrophy
This article has been cited by other articles:
 |
|
 |
|
  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]
|
|
|
|
 |
|
 P. Zahradka Novel Role for Osteopontin in Cardiac Fibrosis Circ. Res., February 15, 2008; 102(3): 270 - 272. [Full Text] [PDF]
|
|
|
|
 |
|
 H. A. Arafat, A. K. Katakam, G. Chipitsyna, Q. Gong, A. R. Vancha, J. Gabbeta, and D. C. Dafoe Osteopontin Protects the Islets and {beta}-Cells from Interleukin-1 {beta}-Mediated Cytotoxicity through Negative Feedback Regulation of Nitric Oxide Endocrinology, February 1, 2007; 148(2): 575 - 584. [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]
|
|
|
|
 |
|
 S. T. Hikita, B. P. Vistica, H. R. Jones, J. R. Keswani, M. M. Watson, V. R. Ericson, G. S. Ayoub, I. Gery, and D. O. Clegg Osteopontin is proinflammatory in experimental autoimmune uveitis. Invest. Ophthalmol. Vis. Sci., October 1, 2006; 47(10): 4435 - 4443. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A K Katakam, G Chipitsyna, Q Gong, A R Vancha, J Gabbeta, and H A Arafat Streptozotocin (STZ) mediates acute upregulation of serum and pancreatic osteopontin (OPN): a novel islet-protective effect of OPN through inhibition of STZ-induced nitric oxide production J. Endocrinol., November 1, 2005; 187(2): 237 - 247. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Satoh, M. Nakamura, T. Akatsu, Y. Shimoda, I. Segawa, and K. Hiramori Myocardial osteopontin expression is associated with collagen fibrillogenesis in human dilated cardiomyopathy Eur J Heart Fail, August 1, 2005; 7(5): 755 - 762. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Ertl and S. Frantz Healing after myocardial infarction Cardiovasc Res, April 1, 2005; 66(1): 22 - 32. [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]
|
|
|
|
|
|
Z. Xie, M. Singh, and K. Singh Osteopontin Modulates Myocardial Hypertrophy in Response to Chronic Pressure Overload in Mice Hypertension, December 1, 2004; 44(6): 826 - 831. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. W.M. Schellings, Y. M. Pinto, and S. Heymans Matricellular proteins in the heart: possible role during stress and remodeling Cardiovasc Res, October 1, 2004; 64(1): 24 - 31. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. H. Goldspink, D. E. Montgomery, L. A. Walker, D. Urboniene, R. D. McKinney, D. L. Geenen, R. J. Solaro, and P. M. Buttrick Protein Kinase C{epsilon} Overexpression Alters Myofilament Properties and Composition During the Progression of Heart Failure Circ. Res., August 20, 2004; 95(4): 424 - 432. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Diez Profibrotic Effects of Angiotensin II in the Heart: A Matter of Mediators Hypertension, June 1, 2004; 43(6): 1164 - 1165. [Full Text] [PDF]
|
|
|
|
|
|
Y. Matsui, N. Jia, H. Okamoto, S. Kon, H. Onozuka, M. Akino, L. Liu, J. Morimoto, S. R. Rittling, D. Denhardt, et al. Role of Osteopontin in Cardiac Fibrosis and Remodeling in Angiotensin II-Induced Cardiac Hypertrophy Hypertension, June 1, 2004; 43(6): 1195 - 1201. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Gao, H. Guo, J. Wei, Z. Mi, P. Wai, and P. C. Kuo S-Nitrosylation of Heterogeneous Nuclear Ribonucleoprotein A/B Regulates Osteopontin Transcription in Endotoxin-stimulated Murine Macrophages J. Biol. Chem., March 19, 2004; 279(12): 11236 - 11243. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. V. Finsen, P. R. Woldbaek, J. Li, J. Wu, T. Lyberg, T. Tonnessen, and G. Christensen Increased syndecan expression following myocardial infarction indicates a role in cardiac remodeling Physiol Genomics, February 13, 2004; 16(3): 301 - 308. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Xie, M. Singh, D. A. Siwik, W. L. Joyner, and K. Singh Osteopontin Inhibits Interleukin-1{beta}-stimulated Increases in Matrix Metalloproteinase Activity in Adult Rat Cardiac Fibroblasts: ROLE OF PROTEIN KINASE C-{zeta} J. Biol. Chem., December 5, 2003; 278(49): 48546 - 48552. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Wang, S. Oparil, J. A. Feng, P. Li, G. Perry, L. B. Chen, M. Dai, S. W.M. John, and Y.-F. Chen Effects of Pressure Overload on Extracellular Matrix Expression in the Heart of the Atrial Natriuretic Peptide-Null Mouse Hypertension, July 1, 2003; 42(1): 88 - 95. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Young, L. Moussa, R. Dilley, and J. W. Funder Early Inflammatory Responses in Experimental Cardiac Hypertrophy and Fibrosis: Effects of 11{beta}-Hydroxysteroid Dehydrogenase Inactivation Endocrinology, March 1, 2003; 144(3): 1121 - 1125. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. R. Heyen, E. R. Blasi, K. Nikula, R. Rocha, H. A. Daust, G. Frierdich, J. F. Van Vleet, P. De Ciechi, E. G. McMahon, and A. E. Rudolph Structural, functional, and molecular characterization of the SHHF model of heart failure Am J Physiol Heart Circ Physiol, November 1, 2002; 283(5): H1775 - H1784. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Stawowy, F. Blaschke, P. Pfautsch, S. Goetze, F. Lippek, B. Wollert-Wulf, E. Fleck, and K. Graf Increased myocardial expression of osteopontin in patients with advanced heart failure Eur J Heart Fail, March 1, 2002; 4(2): 139 - 146. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Mavroidis and Y. Capetanaki Extensive Induction of Important Mediators of Fibrosis and Dystrophic Calcification in Desmin-Deficient Cardiomyopathy Am. J. Pathol., March 1, 2002; 160(3): 943 - 952. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. E. Dostal Regulation of Cardiac Collagen : Angiotensin and Cross-Talk With Local Growth Factors Hypertension, March 1, 2001; 37(3): 841 - 844. [Full Text] [PDF]
|
|
|
|
|
|
C. Kupfahl, D. Pink, K. Friedrich, H. R. Zurbrugg, M. Neuss, C. Warnecke, J. Fielitz, K. Graf, E. Fleck, and V. Regitz-Zagrosek Angiotensin II directly increases transforming growth factor {beta}1 and osteopontin and indirectly affects collagen mRNA expression in the human heart Cardiovasc Res, June 1, 2000; 46(3): 463 - 475. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. O. Boluyt and O. H.L. Bing Matrix gene expression and decompensated heart failure: The aged SHR model Cardiovasc Res, May 1, 2000; 46(2): 239 - 249. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. A. Trueblood, Z. Xie, C. Communal, F. Sam, S. Ngoy, L. Liaw, A. W. Jenkins, J. Wang, D. B. Sawyer, O. H. L. Bing, et al. Exaggerated Left Ventricular Dilation and Reduced Collagen Deposition After Myocardial Infarction in Mice Lacking Osteopontin Circ. Res., May 25, 2001; 88(10): 1080 - 1087. [Abstract] [Full Text] [PDF]
|
|