Published Online
on February 25, 2008

A more recent version of this article appeared on March 11, 2008

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Submitted on May 8, 2007
Accepted on December 24, 2007

Biglycan Is Required for Adaptive Remodeling After Myocardial Infarction

D. Westermann MD, J. Mersmann MD, A. Melchior MS, T. Freudenberger MS, C. Petrik , L. Schaefer PhD, R. Lüllmann-Rauch MD, O. Lettau MS, C. Jacoby PhD, J. Schrader MD, S. M. Brand-Herrman MD, M. F. Young PhD, H. P. Schultheiss MD, B. Levkau MD, H. A. Baba MD, T. Unger MD, K. Zacharowski MD, C. Tschöpe MD, and J. W. Fischer PhD^*

From the Abteilung für Kardiologie und Pneumologie, Charite-Universitätsklinikum Berlin, Campus Benjamin Franklin, Berlin, Germany (D.W., O.L., H.P.S., C.T.); Molecular Cardioprotection and Inflammation Group, Klinik für Anästhesiologie (J.M.) and Molekulare Pharmakologie, Institut für Pharmakologie und Klinische Pharmakologie (A.M., T.F., J.W.F.), Universitätsklinikum Düsseldorf, Düsseldorf, Germany; Center for Cardiovascular Research, Institut für Pharmakologie und Toxikologie, Campus Charite-Mitte, Charite-Universitatsmedizin Berlin, Berlin, Germany (C.P., T.U.); Nephropharmakologie, Allgemeine Pharmakologie und Toxikologie, Klinikum der Johann Wolfgang Goethe Universität Frankfurt, Frankfurt, Germany (L.S.); Institut für Anatomie, Christian-Albrechts-Universität Kiel, Kiel, Germany (R.L.-R.); Institut für Herzkreislauf-Physiologie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany (C.J., J.S.); Leibniz-Institute for Arteriosclerosis Research, Department of Molecular Genetics of Cardiovascular Disease, University of Muenster, Muenster, Germany (S.M.B.-H.); Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Md (M.F.Y.); Institut für Pathophysiologie (B.L.) and Institut für Pathologie (H.A.B.), Universitätsklinikum Essen, Essen, Germany; and Molecular Cardioprotection and Inflammation Group, Department of Anaesthesia, University Hospital Bristol, Bristol Royal Infirmary, Bristol, UK (K.Z.).

^* To whom correspondence should be addressed. E-mail: jens.fischer{at}uni-duesseldorf.de.

Background—After myocardial infarction (MI), extensive remodeling of extracellular matrix contributes to scar formation and preservation of hemodynamic function. On the other hand, adverse and excessive extracellular matrix remodeling leads to fibrosis and impaired function. The present study investigates the role of the small leucine-rich proteoglycan biglycan during cardiac extracellular matrix remodeling and cardiac hemodynamics after MI.

Methods and Results—Experimental MI was induced in wild-type (WT) and bgn^-/0 mice by permanent ligation of the left anterior descending coronary artery. Biglycan expression was strongly increased at 3, 7, and 14 days after MI in WT mice. bgn^-/0 mice showed increased mortality rates after MI as a result of frequent left ventricular (LV) ruptures. Furthermore, tensile strength of the LV derived from bgn^-/0 mice 21 days after MI was reduced as measured ex vivo. Collagen matrix organization was severely impaired in bgn^-/0 mice, as shown by birefringence analysis of Sirius red staining and electron microscopy of collagen fibrils. At 21 days after MI, LV hemodynamic parameters were assessed by pressure-volume measurements in vivo to obtain LV end-diastolic pressure, end-diastolic volume, and end-systolic volume. bgn^-/0 mice were characterized by aggravated LV dilation evidenced by increased LV end-diastolic volume (bgn^-/0, 111±4.2 µL versus WT, 96±4.4 µL; P<0.05) and LV end-diastolic pressure (bgn^-/0, 24±2.7 versus WT, 18±1.8 mm Hg; P<0.05) and severely impaired LV function (EF, bgn^-/0, 12±2% versus WT, 21±4%; P<0.05) 21 days after MI.

Conclusion—Biglycan is required for stable collagen matrix formation of infarct scars and for preservation of cardiac hemodynamic function.

Key words: collagen • myocardial infarction • extracellular matrix • fibrosis • proteoglycans

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Circulation 2008 117: 1247. [Full Text]

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				T. Csont and P. Ferdinandy Letter by Csont and Ferdinandy Regarding Article, "Biglycan Is Required for Adaptive Remodeling After Myocardial Infarction" Circulation, October 7, 2008; 118(15): e521 - e521. [Full Text] [PDF]

				D. Westermann, O. Lettau, H.P. Schultheiss, C. Tschope, J. Mersmann, A. Melchior, T. Freudenberger, J.W. Fischer, C. Petrik, T. Unger, et al. Response to Letter Regarding Article, "Biglycan Is Required for Adaptive Remodeling After Myocardial Infarction" Circulation, October 7, 2008; 118(15): e522 - e522. [Full Text] [PDF]