Biglycan is required for adaptive remodeling after myocardial infarction

被引:106
作者
Westermann, D. [1 ]
Mersmann, J. [2 ]
Melchior, A. [3 ]
Freudenberger, T. [3 ]
Petrik, C. [4 ]
Schaefer, L. [5 ]
Luellmann-Rauch, R. [6 ]
Lettau, O. [1 ]
Jacoby, C. [7 ]
Schrader, J. [7 ]
Brand-Herrmann, S. -M. [8 ]
Young, M. F. [9 ]
Schultheiss, H. P. [1 ]
Levkau, B. [11 ]
Baba, H. A. [10 ]
Unger, T. [4 ]
Zacharowski, K. [12 ]
Tschoepe, C. [1 ]
Fischer, J. W. [3 ]
机构
[1] Charite Univ Klin Berlin, Abt Kardiol & Pneumol, Berlin, Germany
[2] Univ Klin Duesseldorf, Mol Cadioprotect & Inflammat Grp, Anasthesiol Klin, Dusseldorf, Germany
[3] Univ Klin Duesseldorf, Inst Pharmakol & Klin Pharmakol, Klin Mol Pharmacol, Dusseldorf, Germany
[4] Charite Univ Med Berlin, Inst Pharmakol & Toxikol, Cardiovasc Res Ctr, Berlin, Germany
[5] Univ Frankfurt, Nephropharmakol Allgemeine Pharmakol & Toxikol Kl, Frankfurt, Germany
[6] Univ Kiel, Inst Atom, Kiel, Germany
[7] Univ Dusseldorf, Inst Herzkreislauf Physiol, Dusseldorf, Germany
[8] Univ Munster, Dept Mol Genet Cardiovasc Dis, Leibniz Inst Arteriosclerosis Res, Munster, Germany
[9] Natl Inst Dent & Cranofac Res, Craniofac & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA
[10] Univ Klinikum Essen, Inst Pathol, Essen, Germany
[11] Univ Klinikum Essen, Inst Pathophysiol, Essen, Germany
[12] Univ Hosp Bristol, Dept Anaesthesia, Mol Cardioprotect & Inflammat Grp, Bristol, Avon, England
关键词
collagen; myocardial infarction; extracellular matrix; fibrosis; proteoglycans;
D O I
10.1161/CIRCULATIONAHA.107.714147
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 mu L versus WT, 96 +/- 4.4 mu L; 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.
引用
收藏
页码:1269 / 1276
页数:8
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