title: [Mechanisms of extracellular matrix remodeling in dilated cardiomyopathy].
abstract: BACKGROUND
  The mechanisms underlying myocardial remodeling during heart failure have historically been attributed as the consequence of intrinsic changes in cardiac myocytes. Nevertheless, over the last several years, it has become increasingly evident that disruption of extracellular matrix (ECM) homeostasis is also a deciding factor for the progression of myocardial failure.
  Collagens, the chief components of extracellular matrix, are a tightly regulated family of proteins that determine the structural and functional integrity of heart. Synthesis of collagens is regulated at the cellular level while deposition of these proteins depend on a balance between matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinase (TIMPs). Infiltrating inflammatory cells are major producers of MMPs though myocardial cells are also found to synthesize these proteolytic enzymes. However, immune-mediated regulation of myocardial collagen synthesis and deposition during myocardial inflammation remains poorly understood. It seems likely that a paracrine/autorine effect of a repertoire of cytokines on inflammatory cells and myocardial cells may lead to an imbalance in myocardial MMP/TIMP ratio resulting, eventually, in altered myocardial extracellular matrix architecture and contribute significantly to the development of left ventricular remodeling and dysfunction.
  
  
  CONCLUSIONS
  Attempts to delineate the cross-talk between immune cells, myocardial cells and extracellular matrix are important as chronic myocardial inflammation is documented in about 50% of patients with dilated cardiomyopathy.
authors.affiliation: Klinik für Innere Medizin II, Universitätsklinikum Benjamin Franklin, Freie Universität, Berlin, Germany. pauschinger@ukbf.fu-berlin.de
authors.forename: Matthias
authors.initials: M
authors.lastname: Pauschinger
authors.forename: Kumaran
authors.initials: K
authors.lastname: Chandrasekharan
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Peter Lothar
authors.initials: PL
authors.lastname: Schwimmbeck
authors.forename: Michel
authors.initials: M
authors.lastname: Noutsias
authors.forename: Heinz-Peter
authors.initials: HP
authors.lastname: Schultheiss
mesh_terms: D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000378:metabolism; D002478:Cells, Cultured; D002908:Chronic Disease; D003094:Collagen / Q000096:biosynthesis / Q000378:metabolism; D016207:Cytokines / Q000502:physiology; D005109:Extracellular Matrix / Q000378:metabolism / Q000502:physiology; D006333:Heart Failure / Q000209:etiology; D006706:Homeostasis; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009205:Myocarditis / Q000209:etiology; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D018487:Ventricular Dysfunction, Left; D020257:Ventricular Remodeling
chemical_list: D016207:Cytokines; D019714:Tissue Inhibitor of Metalloproteinases; D003094:Collagen; D020782:Matrix Metalloproteinases