doi: 10.1161/CIRCULATIONAHA.108.791699
(Circulation. 2008;118:e521.)
© 2008 American Heart Association, Inc.
Correspondence |
Letter by Csont and Ferdinandy Regarding Article, "Biglycan Is Required for Adaptive Remodeling After Myocardial Infarction"
Cardiovascular Research Group, Department of Biochemistry, University of Szeged, Pharmahungary Group, Szeged, Hungary
We read with great interest the article by Westermann et al1 in which the authors showed that biglycan expression was strongly increased in the myocardium after permanent coronary occlusion in wild-type mice. In the hearts of bgn–/0 mice 21 days after coronary occlusion, however, collagen matrix organization was impaired, and several parameters of left ventricular function were deteriorated. Furthermore, these animals showed increased mortality rates after infarction. The authors conclude that the complete absence of biglycan is deleterious and prevents the establishment of a stable infarct scar and hemodynamic adaptation, suggesting that biglycan is required for proper infarct healing.
Although the observations of the authors are most valuable, the major conclusion of the authors1 is based solely on cardiac functional and collagen histochemistry data in bgn–/0 mice. Therefore, it is our opinion that there may be alternative explanations for the findings. For instance, it cannot be excluded that overexpression of decorin and other proteoglycans, as well as increased matrix metalloproteinase activities, as shown by Westermann et al,1 contributed to the observations in bgn–/0 mice. Furthermore, some methodological issues, such as the low n number of some data (especially ventricular ruptures) and the measurement of infarct size and area at risk by evans blue/nitroblue tetrazolium staining 7 days after coronary occlusion when granulocytes, monocytes, and fibroblasts migrate into the infarcted area, thereby producing artifacts, do not strengthen the authors conclusions. Additional data in biglycan overexpressing mice and/or administration of exogenous biglycan would have greatly strengthened the interesting conclusions of the authors and could have given some insight into the mechanism of the deterioration of myocardial function in the absence of biglycan.
Recent results showed that proteoglycans are not merely rigid components of the extracellular matrix, but play an important role in deposition of collagens, activation and inactivation of cytokines and growth factors. As the authors1 pointed out in their article, it has been reported previously by others that biglycan and decorin are induced in the infarcted myocardium. Furthermore, increased expression of biglycan mRNA in pressure-overloaded rat hearts during remodeling has been also shown by others.2 However, Ahmed et al3 showed that treatment of infarcted rats with the AT1 receptor antagonist losartan, an intervention well documented to attenuate cardiac remodeling in heart failure, prevented the increase of myocardial biglycan. This result seems to be against the conclusion of the study of Westerman et al;1 however, it is not discussed in their article. We have recently shown4 that in the heart of biglycan-overexpressing mice, a number of well-known cardioprotective genes and proteins,5 such as nitric oxide synthases, mitogen-activated protein kinases, and transforming growth factor β, etc, that might lead to cardioprotection against myocardial infarction, are overexpressed. These observations4 may support the present results of the authors.1
Thus, with these comments, it is our opinion that the conclusions of the authors are somewhat premature regarding the role of biglycan in myocardial infarction–induced heart failure. We would urge investigators to prove the potential beneficial effect of biglycan by either administration of exogenous biglycan or enhancement of biglycan activity by genetic manipulations or induction of biglycan synthesis. Nevertheless, biglycan could be an interesting new target for development of cardioprotective therapy.
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Acknowledgments |
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Sources of Funding
The authors received a grant from National Research and Technology Office (NKFPA1–2006–029).
Disclosures
The authors are inventors of an international patent application, "Use of biglycan or enhancers of biglycan activity in the preparation of pharmaceutical compositions" (PCT/HU2008/000003, January 10, 2008; primary filing, January 11, 2007). Dr Ferdinandy is an owner and Dr Csont is involved in the management of a pharmaceutical/biotechnological company.
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 Top References |
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1. Westermann D, Mersmann J, Melchior A, Freudenberger T, Petrik C, Schaefer L, Lullmann-Rauch R, Lettau O, Jacoby C, Schrader J, Brand-Herrman SM, Young MF, Schultheiss HP, Levkau B, Baba HA, Unger T, Zacharowski K, Tschope C, Fischer JW. Biglycan is required for adaptive remodeling after myocardial infarction. Circulation. 2008; 117: 1269–1276.
2. Ayada Y, Kusachi S, Murakami T, Hirohata S, Takemoto S, Komatsubara I, Hayashi J, Iwabu A, Ninomiya Y, Tsuji T. Increased expression of biglycan mRNA in pressure-overloaded rat heart. Clin Exp Hypertens. 2001; 23: 633–643.[CrossRef][Medline] [Order article via Infotrieve]
3. Ahmed MS, Oie E, Vinge LE, Yndestad A, Andersen GG, Andersson Y, Attramadal T, Attramadal H. Induction of myocardial biglycan in heart failure in rats-an extracellular matrix component targeted by AT(1) receptor antagonism. Cardiovasc Res. 2003; 60: 557–568.
4. Bereczki E, Gonda S, Csont T, Korpos E, Zvara A, Ferdinandy P, Santha M. Overexpression of biglycan in the heart of transgenic mice: an antibody microarray study. J Proteome Res. 2007; 6: 854–861.[CrossRef][Medline] [Order article via Infotrieve]
5. Ferdinandy P, Schulz R, Baxter GF. Interaction of cardiovascular risk factors with myocardial ischemia/reperfusion injury, preconditioning, and postconditioning. Pharmacol Rev. 2007; 59: 418–458.
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