Dilated cardiomyopathy is associated with an increase in the type I/type III collagen ratio: a quantitative assessment

Department of Cardiovascular Pathology, Academic Medical Center, Amsterdam, The Netherlands.

OBJECTIVES. The aim of this study was to quantify total collagen and the type I/type III collagen ratio and their localization in hearts with dilated cardiomyopathy. BACKGROUND. Patients with dilated cardiomyopathy have an increase in intramyocardial fibrillar collagen. Types I and III are the main constituents and have different physical properties that may affect cardiac compliance. METHODS. Nineteen hearts with dilated cardiomyopathy were studied (17 cardiac explants, 2 hearts obtained at autopsy) and compared with reference hearts. Total collagen was determined by hydroxyproline analysis. Collagen types I and III were analyzed using the cyanogen bromide method and immunohistochemical analysis followed by microdensitophotometric quantification. Localization of collagen types I and III was established at the light and electron microscopic levels. Immunoelectron microscopy provided information regarding their localization. RESULTS. Total collagen and the collagen type I/type III ratio were increased in hearts with dilated cardiomyopathy (p < 0.05). Electron microscopy showed a diffuse increase in collagen fibrils in the endomysium; the perimysium showed an inhomogeneous increase. Collagen fibrils were thicker, and fibrous long-spacing collagen occurred in the endomysium. Immunoelectron microscopic findings confirmed an increase in type I collagen. CONCLUSIONS. Hearts with dilated cardiomyopathy have a statistically significant increase in the collagen type I/type III ratio. The changes occur in the endomysium and perimysium, although with differences in distribution. These changes in intramyocardial collagen may be clinically relevant because they may affect cardiac rigidity and, therefore, eventually may render the heart less compliant. Further studies are needed to evaluate at what point in the course of the disease these changes appear.

This article has been cited by other articles:

				J. R. Venugopal, M. P. Prabhakaran, S. Mukherjee, R. Ravichandran, K. Dan, and S. Ramakrishna Biomaterial strategies for alleviation of myocardial infarction J R Soc Interface, January 7, 2012; 9(66): 1 - 19. [Abstract] [Full Text] [PDF]

				C. Galvez-Monton, C. Prat-Vidal, S. Roura, J. Farre, C. Soler-Botija, A. Llucia-Valldeperas, I. Diaz-Guemes, F. M. Sanchez-Margallo, A. Aris, and A. Bayes-Genis Transposition of a pericardial-derived vascular adipose flap for myocardial salvage after infarct Cardiovasc Res, September 1, 2011; 91(4): 659 - 667. [Abstract] [Full Text] [PDF]

				N. Mewton, C. Y. Liu, P. Croisille, D. Bluemke, and J. A. C. Lima Assessment of Myocardial Fibrosis With Cardiovascular Magnetic Resonance J. Am. Coll. Cardiol., February 22, 2011; 57(8): 891 - 903. [Abstract] [Full Text] [PDF]

				T. G. Voloshenyuk and J. D. Gardner Estrogen improves TIMP-MMP balance and collagen distribution in volume-overloaded hearts of ovariectomized females Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2010; 299(2): R683 - R693. [Abstract] [Full Text] [PDF]

				E. M. Kanoupakis, E. G. Manios, E. M. Kallergis, H. E. Mavrakis, C. A. Goudis, I. G. Saloustros, M. E. Milathianaki, G. I. Chlouverakis, and P. E. Vardas Serum Markers of Collagen Turnover Predict Future Shocks in Implantable Cardioverter-Defibrillator Recipients With Dilated Cardiomyopathy on Optimal Treatment J. Am. Coll. Cardiol., June 15, 2010; 55(24): 2753 - 2759. [Abstract] [Full Text] [PDF]

				G. J. Mak, M. T. Ledwidge, C. J. Watson, D. M. Phelan, I. R. Dawkins, N. F. Murphy, A. K. Patle, J. A. Baugh, and K. M. McDonald Natural History of Markers of Collagen Turnover in Patients With Early Diastolic Dysfunction and Impact of Eplerenone J. Am. Coll. Cardiol., October 27, 2009; 54(18): 1674 - 1682. [Abstract] [Full Text] [PDF]

				M. Wilson, R. O'Hanlon, S. Prasad, S. Basavarajaiah, N. Stephens, R. Senior, A. Shaw, S. Sharma, and G. Whyte Myocardial fibrosis in an veteran endurance athlete BMJ Case Reports, August 17, 2009; 2009(aug17_1): bcr1220081345 - bcr1220081345. [Abstract] [Full Text]

				G. Whyte, M. Sheppard, K. George, R. Shave, S. Prasad, R. O'Hanlon, and S. Sharma Post-mortem evidence of idiopathic left ventricular hypertrophy and idiopathic interstitial myocardial fibrosis: is exercise the cause? BMJ Case Reports, February 2, 2009; 2009(jan27_1): bcr0820080758 - bcr0820080758. [Abstract] [Full Text]

				W. A. Jaber, C. Maniu, J. Krysiak, B. P. Shapiro, D. M. Meyer, W. A. Linke, and M. M. Redfield Titin Isoforms, Extracellular Matrix, and Global Chamber Remodeling in Experimental Dilated Cardiomyopathy: Functional Implications and Mechanistic Insight Circ Heart Fail, September 1, 2008; 1(3): 192 - 199. [Abstract] [Full Text] [PDF]

				A. R. Kompa, F. See, D. A. Lewis, A. Adrahtas, D. M. Cantwell, B. H. Wang, and H. Krum Long-Term but Not Short-Term p38 Mitogen-Activated Protein Kinase Inhibition Improves Cardiac Function and Reduces Cardiac Remodeling Post-Myocardial Infarction J. Pharmacol. Exp. Ther., June 1, 2008; 325(3): 741 - 750. [Abstract] [Full Text] [PDF]

				G Whyte, M Sheppard, K George, R Shave, M Wilson, S Prasad, R O'Hanlon, and S Sharma Post-mortem evidence of idiopathic left ventricular hypertrophy and idiopathic interstitial myocardial fibrosis: is exercise the cause? Br. J. Sports Med., April 1, 2008; 42(4): 304 - 305. [Abstract] [Full Text] [PDF]

				H. Blangy, N. Sadoul, B. Dousset, A. Radauceanu, R. Fay, E. Aliot, and F. Zannad Serum BNP, hs-C-reactive protein, procollagen to assess the risk of ventricular tachycardia in ICD recipients after myocardial infarction Europace, September 1, 2007; 9(9): 724 - 729. [Abstract] [Full Text] [PDF]

				G. L. Brower, J. D. Gardner, M. F. Forman, D. B. Murray, T. Voloshenyuk, S. P. Levick, and J. S. Janicki The relationship between myocardial extracellular matrix remodeling and ventricular function Eur J Cardiothorac Surg, October 1, 2006; 30(4): 604 - 610. [Abstract] [Full Text] [PDF]

				J. J. Gavira, M. Perez-Ilzarbe, G. Abizanda, A. Garcia-Rodriguez, J. Orbe, J. A. Paramo, M. Belzunce, G. Rabago, J. Barba, J. Herreros, et al. A comparison between percutaneous and surgical transplantation of autologous skeletal myoblasts in a swine model of chronic myocardial infarction Cardiovasc Res, September 1, 2006; 71(4): 744 - 753. [Abstract] [Full Text] [PDF]

				H. Milting, A. Kassner, L. Arusoglu, H. E. Meyer, M. Morshuis, R. Brendel, B. Klauke, A. El Banayosy, and R. Korfer Influence of ACE-inhibition and mechanical unloading on the regulation of extracellular matrix proteins in the myocardium of heart transplantation candidates bridged by ventricular assist devices Eur J Heart Fail, May 1, 2006; 8(3): 278 - 283. [Abstract] [Full Text] [PDF]

				J. Shigeyama, Y. Yasumura, A. Sakamoto, Y. Ishida, T. Fukutomi, M. Itoh, K. Miyatake, and M. Kitakaze Increased gene expression of collagen Types I and III is inhibited by {beta}-receptor blockade in patients with dilated cardiomyopathy Eur. Heart J., December 2, 2005; 26(24): 2698 - 2705. [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]

				S. Klotz, R. F. Foronjy, M. L. Dickstein, A. Gu, I. M. Garrelds, A.H. Jan Danser, M. C. Oz, J. D'Armiento, and D. Burkhoff Mechanical Unloading During Left Ventricular Assist Device Support Increases Left Ventricular Collagen Cross-Linking and Myocardial Stiffness Circulation, July 19, 2005; 112(3): 364 - 374. [Abstract] [Full Text] [PDF]

				A Brooks, V Schinde, A C Bateman, and P J Gallagher Interstitial fibrosis in the dilated non-ischaemic myocardium Heart, October 1, 2003; 89(10): 1255 - 1256. [Full Text] [PDF]

				Y. Wu, S. P. Bell, K. Trombitas, C. C. Witt, S. Labeit, M. M. LeWinter, and H. Granzier Changes in Titin Isoform Expression in Pacing-Induced Cardiac Failure Give Rise to Increased Passive Muscle Stiffness Circulation, September 10, 2002; 106(11): 1384 - 1389. [Abstract] [Full Text] [PDF]

				P. Stawowy, F. Blaschke, P. Pfautsch, S. Goetze, F. Lippek, B. Wollert-Wulf, E. Fleck, and K. Graf Increased myocardial expression of osteopontin in patients with advanced heart failure Eur J Heart Fail, March 1, 2002; 4(2): 139 - 146. [Abstract] [Full Text] [PDF]

				N. Nishikawa, T. Masuyama, K. Yamamoto, Y. Sakata, T. Mano, T. Miwa, M. Sugawara, and M. Hori Long-term administration of amlodipine prevents decompensation to diastolic heart failure in hypertensive rats J. Am. Coll. Cardiol., November 1, 2001; 38(5): 1539 - 1545. [Abstract] [Full Text] [PDF]

				P. Rouet-Benzineb, J.-M. Buhler, P. Dreyfus, A. Delcourt, R. Dorent, J. Perennec, B. Crozatier, A. Harf, and C. Lafuma Altered balance between matrix gelatinases (MMP-2 and MMP-9) and their tissue inhibitors in human dilated cardiomyopathy: potential role of MMP-9 in myosin-heavy chain degradation Eur J Heart Fail, December 17, 1999; 1(4): 337 - 352. [Abstract] [Full Text] [PDF]

				M d. L. Higuchi, S Fukasawa, T De Brito, L C Parzianello, G Bellotti, and J A F Ramires Different microcirculatory and interstitial matrix patterns in idiopathic dilated cardiomyopathy and Chagas' disease: a three dimensional confocal microscopy study Heart, September 1, 1999; 82(3): 279 - 285. [Abstract] [Full Text] [PDF]

				M. Pauschinger, D. Knopf, S. Petschauer, A. Doerner, W. Poller, P. L. Schwimmbeck, U. Kuhl, and H.-P. Schultheiss Dilated Cardiomyopathy Is Associated With Significant Changes in Collagen Type I/III ratio Circulation, June 1, 1999; 99(21): 2750 - 2756. [Abstract] [Full Text] [PDF]

				G. Hasenfuss Animal models of human cardiovascular disease, heart failure and hypertrophy Cardiovasc Res, July 1, 1998; 39(1): 60 - 76. [Abstract] [Full Text] [PDF]

				M. Pauschinger, A. Doerner, A. Remppis, R. Tannhauser, U. Kuhl, and H.-P. Schultheiss Differential myocardial abundance of collagen type I and type III mRNA in dilated cardiomyopathy: effects of myocardial inflammation Cardiovasc Res, January 1, 1998; 37(1): 123 - 129. [Abstract] [Full Text] [PDF]