Circulation Research. 2001;88:1080-1087
Published online before print May 10, 2001, doi: 10.1161/hh1001.090842
Published online before print May 10, 2001, doi: 10.1161/hh1001.090842
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2001 American Heart Association, Inc.
Integrative Physiology |
Exaggerated Left Ventricular Dilation and Reduced Collagen Deposition After Myocardial Infarction in Mice Lacking Osteopontin
From the Myocardial Biology Unit and Cardiovascular Section, Boston Medical Center, Boston Veterans Affairs Medical Center and Boston University School of Medicine (N.A.T., Z.X., C.C., F.S., S.N., J.W., D.B.S., O.H.L.B., C.S.A., W.S.C., K.S.), Boston, Mass; the Maine Medical Research Center (L.L.), South Portland, Maine; and Bates College (A.W.J.), Lewiston, Maine.
Correspondence to Krishna Singh, PhD, Myocardial Biology Unit, 650 Albany St, X-706, Boston, MA 02118. E-mail krishna.singh{at}bmc.org
Abstract—Osteopontin
(OPN), an extracellular matrix protein, is expressed in the
myocardium with hypertrophy and failure. We
tested the hypothesis that OPN plays a role in left
ventricular (LV) remodeling after myocardial infarction
(MI). Accordingly, OPN expression and LV structural and functional
remodeling were determined in wild-type (WT) and OPN knockout (KO) mice
4 weeks after MI. Northern analysis showed increased OPN
expression in the infarcted region, peaking 3 days after MI and
gradually decreasing over the next 28 days. In the remote LV, OPN
expression was biphasic, with peaks at 3 and 28 days. In situ
hybridization and immunohistochemical analyses showed increased
OPN mRNA and protein primarily in the interstitium. Infarct size, heart
weight, and survival were similar in KO and WT mice after MI
(P=NS), whereas the lung wet
weight/dry weight ratio was increased in the KO mice
(P<0.005 versus sham-operated
mice). Peak LV developed pressure was reduced to a similar degree after
MI in the KO and WT mice. The number of terminal
deoxynucleotidyl transferase–mediated dUTP nick
end-labeling (TUNEL)-positive myocytes was similar in KO and WT mice
after MI. In contrast, post-MI LV chamber dilation was approximately
twice as great in KO versus WT mice
(P<0.001). Myocyte length
increased after MI in WT mice
(P<0.001) but not in KO mice.
Electron microscopy showed increased collagen content in WT mice after
MI but not in KO mice after MI. Type I collagen content was increased
3-fold and 7-fold in remote and infarcted regions, respectively,
of WT hearts after MI but not in KO hearts
(P<0.01 versus WT hearts).
Likewise, Northern analyses showed increased collagen
I(
1) mRNA after MI in remote regions of WT
hearts but not in KO hearts. Thus, increased OPN expression plays an
important role in regulating post-MI LV remodeling, at least in part,
by promoting collagen synthesis and accumulation.
Key Words: extracellular matrix proteins • osteopontin • collagen • myocyte slippage • myocyte elongation
This article has been cited by other articles:
 |
|
 |
|
  M. Kohan, R. Breuer, and N. Berkman Osteopontin Induces Airway Remodeling and Lung Fibroblast Activation in a Murine Model of Asthma Am. J. Respir. Cell Mol. Biol., September 1, 2009; 41(3): 290 - 296. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Heymans, E. Hirsch, S. D. Anker, P. Aukrust, J.-L. Balligand, J. W. Cohen-Tervaert, H. Drexler, G. Filippatos, S. B. Felix, L. Gullestad, et al. Inflammation as a therapeutic target in heart failure? A scientific statement from the Translational Research Committee of the Heart Failure Association of the European Society of Cardiology Eur J Heart Fail, February 1, 2009; 11(2): 119 - 129. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. W.M. Schellings, D. Vanhoutte, M. Swinnen, J. P. Cleutjens, J. Debets, R. E.W. van Leeuwen, J. d'Hooge, F. Van de Werf, P. Carmeliet, Y. M. Pinto, et al. Absence of SPARC results in increased cardiac rupture and dysfunction after acute myocardial infarction J. Exp. Med., January 16, 2009; 206(1): 113 - 123. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Caglayan, B. Stauber, A. R. Collins, C. J. Lyon, F. Yin, J. Liu, S. Rosenkranz, E. Erdmann, L. E. Peterson, R. S. Ross, et al. Differential Roles of Cardiomyocyte and Macrophage Peroxisome Proliferator-Activated Receptor {gamma} in Cardiac Fibrosis Diabetes, September 1, 2008; 57(9): 2470 - 2479. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T.-Y. Chun, P. N. Chander, J.-W. Kim, J. H. Pratt, and C. T. Stier Jr. Aldosterone, but not angiotensin II, increases profibrotic factors in kidney of adrenalectomized stroke-prone spontaneously hypertensive rats Am J Physiol Endocrinol Metab, August 1, 2008; 295(2): E305 - E312. [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]
|
|
|
|
 |
|
 K.-i. Miyazaki, Y. Okada, O. Yamanaka, A. Kitano, K. Ikeda, S. Kon, T. Uede, S. R. Rittling, D. T. Denhardt, W. W.-Y. Kao, et al. Corneal Wound Healing in an Osteopontin-Deficient Mouse Invest. Ophthalmol. Vis. Sci., April 1, 2008; 49(4): 1367 - 1375. [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]
|
|
|
|
|
|
Y. Lenga, A. Koh, A. S. Perera, C. A. McCulloch, J. Sodek, and R. Zohar Osteopontin Expression Is Required for Myofibroblast Differentiation Circ. Res., February 15, 2008; 102(3): 319 - 327. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Hu, A. Dandapat, J. Chen, Y. Fujita, N. Inoue, Y. Kawase, K.-i. Jishage, H. Suzuki, T. Sawamura, and J. L. Mehta LOX-1 deletion alters signals of myocardial remodeling immediately after ischemia-reperfusion Cardiovasc Res, November 1, 2007; 76(2): 292 - 302. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Deng, B. Kulle, M. Hosseini, G. Schluter, G. Hasenfuss, L. Wojnowski, and A. Schmidt Dystrophin-deficiency increases the susceptibility to doxorubicin-induced cardiotoxicity Eur J Heart Fail, October 1, 2007; 9(10): 986 - 994. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Krishnamurthy, V. Subramanian, M. Singh, and K. Singh {beta}1 Integrins Modulate {beta}-Adrenergic Receptor-Stimulated Cardiac Myocyte Apoptosis and Myocardial Remodeling Hypertension, April 1, 2007; 49(4): 865 - 872. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Vanhoutte, M. W.M. Schellings, M. Gotte, M. Swinnen, V. Herias, M. K. Wild, D. Vestweber, E. Chorianopoulos, V. Cortes, A. Rigotti, et al. Increased Expression of Syndecan-1 Protects Against Cardiac Dilatation and Dysfunction After Myocardial Infarction Circulation, January 30, 2007; 115(4): 475 - 482. [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]
|
|
|
|
 |
|
 P Krishnamurthy, V Subramanian, M Singh, and K Singh Deficiency of {beta}1 integrins results in increased myocardial dysfunction after myocardial infarction Heart, September 1, 2006; 92(9): 1309 - 1315. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Sodek, A. P. Batista Da Silva, and R. Zohar Osteopontin and Mucosal Protection Journal of Dental Research, May 1, 2006; 85(5): 404 - 415. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Vanhoutte, M. Schellings, Y. Pinto, and S. Heymans Relevance of matrix metalloproteinases and their inhibitors after myocardial infarction: A temporal and spatial window Cardiovasc Res, February 15, 2006; 69(3): 604 - 613. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Yano, T. Miura, P. Whittaker, T. Miki, J. Sakamoto, Y. Nakamura, Y. Ichikawa, Y. Ikeda, H. Kobayashi, K. Ohori, et al. Macrophage Colony-Stimulating Factor Treatment After Myocardial Infarction Attenuates Left Ventricular Dysfunction by Accelerating Infarct Repair J. Am. Coll. Cardiol., February 7, 2006; 47(3): 626 - 634. [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]
|
|
|
|
|
|
N. G. Frangogiannis, G. Ren, O. Dewald, P. Zymek, S. Haudek, A. Koerting, K. Winkelmann, L. H. Michael, J. Lawler, and M. L. Entman Critical Role of Endogenous Thrombospondin-1 in Preventing Expansion of Healing Myocardial Infarcts Circulation, June 7, 2005; 111(22): 2935 - 2942. [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]
|
|
|
|
|
|
Y. Sugano, T. Anzai, T. Yoshikawa, Y. Maekawa, T. Kohno, K. Mahara, K. Naito, and S. Ogawa Granulocyte colony-stimulating factor attenuates early ventricular expansion after experimental myocardial infarction Cardiovasc Res, February 1, 2005; 65(2): 446 - 456. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Giacopelli, R. Marciano, A. Pistorio, P. Catarsi, S. Canini, G. Karsenty, and R. Ravazzolo Polymorphisms in the osteopontin promoter affect its transcriptional activity Physiol Genomics, December 15, 2004; 20(1): 87 - 96. [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]
|
|
|
|
|
|
Y. Maekawa, T. Anzai, T. Yoshikawa, Y. Sugano, K. Mahara, T. Kohno, T. Takahashi, and S. Ogawa Effect of granulocyte-macrophage colony-stimulating factor inducer on left ventricular remodeling after acute myocardial infarction J. Am. Coll. Cardiol., October 6, 2004; 44(7): 1510 - 1520. [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]
|
|
|
|
|
|
R. Zohar, B. Zhu, P. Liu, J. Sodek, and C. A. McCulloch Increased cell death in osteopontin-deficient cardiac fibroblasts occurs by a caspase-3-independent pathway Am J Physiol Heart Circ Physiol, October 1, 2004; 287(4): H1730 - H1739. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S Ross Molecular and mechanical synergy: cross-talk between integrins and growth factor receptors Cardiovasc Res, August 15, 2004; 63(3): 381 - 390. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Hilfiker-Kleiner, A. Hilfiker, M. Fuchs, K. Kaminski, A. Schaefer, B. Schieffer, A. Hillmer, A. Schmiedl, Z. Ding, E. Podewski, et al. Signal Transducer and Activator of Transcription 3 Is Required for Myocardial Capillary Growth, Control of Interstitial Matrix Deposition, and Heart Protection From Ischemic Injury Circ. Res., July 23, 2004; 95(2): 187 - 195. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Nian, P. Lee, N. Khaper, and P. Liu Inflammatory Cytokines and Postmyocardial Infarction Remodeling Circ. Res., June 25, 2004; 94(12): 1543 - 1553. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Berman, D. Serlin, X. Li, G. Whitley, J. Hayes, D. C. Rishikof, D. A. Ricupero, L. Liaw, M. Goetschkes, and A. W. O'Regan Altered bleomycin-induced lung fibrosis in osteopontin-deficient mice Am J Physiol Lung Cell Mol Physiol, June 1, 2004; 286(6): L1311 - L1318. [Abstract] [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]
|
|
|
|
|
|
A. R. Collins, J. Schnee, W. Wang, S. Kim, M. C. Fishbein, D. Bruemmer, R. E. Law, S. Nicholas, R. S. Ross, and W. A. Hsueh Osteopontin modulates angiotensin II- induced fibrosis in the intact murine heart J. Am. Coll. Cardiol., May 5, 2004; 43(9): 1698 - 1705. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. K Shieh, E. Kotlyar, and F. Sam Aldosterone and cardiovascular remodelling: focus on myocardial failure Journal of Renin-Angiotensin-Aldosterone System, March 1, 2004; 5(1): 3 - 13. [Abstract] [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]
|
|
|
|
 |
|
 J. D. Porter, A. P. Merriam, P. Leahy, B. Gong, and S. Khanna Dissection of temporal gene expression signatures of affected and spared muscle groups in dystrophin-deficient (mdx) mice Hum. Mol. Genet., August 1, 2003; 12(15): 1813 - 1821. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Hirata, S. Masuda, T. Tamura, K. Kai, K. Ojima, A. Fukase, K. Motoyoshi, K. Kamakura, Y. Miyagoe-Suzuki, and S.'i. Takeda Expression Profiling of Cytokines and Related Genes in Regenerating Skeletal Muscle after Cardiotoxin Injection: A Role for Osteopontin Am. J. Pathol., July 1, 2003; 163(1): 203 - 215. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. L. Myers, K. J. Harmon, V. Lindner, and L. Liaw Alterations of Arterial Physiology in Osteopontin-Null Mice Arterioscler Thromb Vasc Biol, June 1, 2003; 23(6): 1021 - 1028. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. N. Haslett, D. Sanoudou, A. T. Kho, R. R. Bennett, S. A. Greenberg, I. S. Kohane, A. H. Beggs, and L. M. Kunkel Gene expression comparison of biopsies from Duchenne muscular dystrophy (DMD) and normal skeletal muscle PNAS, November 12, 2002; 99(23): 15000 - 15005. [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]
|
|
|
|
|
|
D. Fraccarollo, P. Galuppo, J. Bauersachs, and G. Ertl Collagen accumulation after myocardial infarction: effects of ETA receptor blockade and implications for early remodeling: Presented in part at the 72nd Scientific Session of the American Heart Association, Atlanta, GA, USA, November 7-10, 1999, and published in abstract form (Circulation 1999;100(Suppl. 1):562) Cardiovasc Res, June 1, 2002; 54(3): 559 - 567. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Teerlink and M. B. Ratcliffe Ventricular remodeling surgery for heart failure: small animals and how to measure an improvement in ventricular function Ann. Thorac. Surg., May 1, 2002; 73(5): 1368 - 1370. [Full Text] [PDF]
|
|
|
|
|
|
J. D. Porter, S. Khanna, H. J. Kaminski, J. S. Rao, A. P. Merriam, C. R. Richmonds, P. Leahy, J. Li, W. Guo, and F. H. Andrade A chronic inflammatory response dominates the skeletal muscle molecular signature in dystrophin-deficient mdx mice Hum. Mol. Genet., February 1, 2002; 11(3): 263 - 272. [Abstract] [Full Text] [PDF]
|
|