Myocardial osteopontin expression coincides with the development of heart failure.

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 (approximately 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 (approximately 1.9-fold) in left ventricular myocardium from nonfailing aortic-banded rats with pressure-overload hypertrophy but was markedly increased (approximately 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.

[1]  N. Takahashi,et al.  Nitric oxide, atrial natriuretic peptide, and cyclic GMP inhibit the growth-promoting effects of norepinephrine in cardiac myocytes and fibroblasts. , 1998, The Journal of clinical investigation.

[2]  M. Creager,et al.  Increased sensitivity to nitric oxide synthase inhibition in patients with heart failure: potentiation of beta-adrenergic inotropic responsiveness. , 1998, Circulation.

[3]  Lorell Bh Transition from hypertrophy to failure. , 1997 .

[4]  K. Weber,et al.  Extracellular matrix remodeling in heart failure: a role for de novo angiotensin II generation. , 1997, Circulation.

[5]  C. H. Conrad,et al.  Effect of angiotensin-converting enzyme inhibition on myocardial fibrosis and function in hypertrophied and failing myocardium from the spontaneously hypertensive rat. , 1997, Circulation.

[6]  E. Fleck,et al.  Myocardial osteopontin expression is associated with left ventricular hypertrophy. , 1997, Circulation.

[7]  C. H. Conrad,et al.  Localization of alpha1(I) collagen mRNA in myocardium from the spontaneously hypertensive rat during the transition from compensated hypertrophy to failure. , 1997, Journal of molecular and cellular cardiology.

[8]  A. Peri,et al.  Potential roles of osteopontin and αVβ3 integrin in the development of coronary artery restenosis after angioplasty , 1997 .

[9]  O. H. Bing,et al.  Endogenous retroviral transcripts in myocytes from spontaneously hypertensive rats. , 1997, Hypertension.

[10]  M. Pfeffer,et al.  The transition to failure in the spontaneously hypertensive rat. , 1997, American journal of hypertension.

[11]  B. Lorell Transition from hypertrophy to failure. , 1997, Circulation.

[12]  S. Moncada,et al.  Expression of inducible nitric oxide synthase in human heart failure. , 1997, Circulation.

[13]  W A Hsueh,et al.  Osteopontin is produced by rat cardiac fibroblasts and mediates A(II)-induced DNA synthesis and collagen gel contraction. , 1996, The Journal of clinical investigation.

[14]  E. Lakatta,et al.  The ageing spontaneously hypertensive rat as a model of the transition from stable compensated hypertrophy to heart failure. , 1995, European heart journal.

[15]  J. Balligand,et al.  Glucocorticoids Increase Osteopontin Expression in Cardiac Myocytes and Microvascular Endothelial Cells , 1995, The Journal of Biological Chemistry.

[16]  T. Borg,et al.  Role of the α1β1 integrin complex in collagen gel contraction in vitro by fibroblasts , 1995 .

[17]  J. Rottman,et al.  Osteopontin expression is increased in the heritable cardiomyopathy of Syrian hamsters. , 1995, Circulation.

[18]  S. Schwartz,et al.  Molecular and cellular biology of osteopontin Potential role in cardiovascular disease. , 1995, Trends in cardiovascular medicine.

[19]  J. S. Janicki,et al.  Prevention of angiotensin II induced myocyte necrosis and coronary vascular damage by lisinopril and losartan in the rat. , 1995, Cardiovascular research.

[20]  C. H. Conrad,et al.  The spontaneously hypertensive rat as a model of the transition from compensated left ventricular hypertrophy to failure. , 1995, Journal of molecular and cellular cardiology.

[21]  C. H. Conrad,et al.  Myocardial fibrosis and stiffness with hypertrophy and heart failure in the spontaneously hypertensive rat. , 1995, Circulation.

[22]  S M Schwartz,et al.  Macrophages express osteopontin during repair of myocardial necrosis. , 1994, The American journal of pathology.

[23]  C. H. Conrad,et al.  Alterations in cardiac gene expression during the transition from stable hypertrophy to heart failure. Marked upregulation of genes encoding extracellular matrix components. , 1994, Circulation research.

[24]  C. Alpers,et al.  Osteopontin expression in angiotensin II-induced tubulointerstitial nephritis. , 1994, Kidney international.

[25]  D. Denhardt,et al.  Osteopontin: a protein with diverse functions , 1993, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[26]  J. Balligand,et al.  Abnormal contractile function due to induction of nitric oxide synthesis in rat cardiac myocytes follows exposure to activated macrophage-conditioned medium. , 1993, The Journal of clinical investigation.

[27]  J. Sodek,et al.  Developmental expression of osteopontin (OPN) mRNA in rat tissues: evidence for a role for OPN in bone formation and resorption. , 1993, Matrix.

[28]  A. Mukherjee,et al.  Differential processing of osteopontin transcripts in rat kidney- and osteoblast-derived cell lines. , 1992, The Journal of biological chemistry.

[29]  F. Blattner,et al.  Structural and functional studies of the early T lymphocyte activation 1 (Eta-1) gene. Definition of a novel T cell-dependent response associated with genetic resistance to bacterial infection , 1989, The Journal of experimental medicine.

[30]  W. Butler,et al.  The nature and significance of osteopontin. , 1989, Connective tissue research.

[31]  P. Chomczyński,et al.  Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. , 1987, Analytical biochemistry.

[32]  D. Heinegård,et al.  Cloning and sequence analysis of rat bone sialoprotein (osteopontin) cDNA reveals an Arg-Gly-Asp cell-binding sequence. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[33]  M. Pfeffer,et al.  Regression of left ventricular hypertrophy and prevention of left ventricular dysfunction by captopril in the spontaneously hypertensive rat. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[34]  B. Posner,et al.  Ribonucleic acid synthesis in experimental cardiac hypertrophy in rats. II. Aspects of regulation. , 1968, Circulation research.

[35]  B. Posner,et al.  Ribonucleic Acid Synthesis in Experimental Cardiac Hypertrophy in Rats: I. Characterization and Kinetics of Labeling , 1968, Circulation research.