Is TGF-β1 (Transforming Growth Factor-β1) an Enabler of Myofibroblast–Cardiomyocyte Cross Talk?
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Arrhythmias and sudden cardiac arrest are among the most important causes of morbidity and mortality in the developed world, but their underlying causes remain elusive. Arrhythmogenic substrates may be established by ischemia, infarction, heart failure, drugs, and genetic mutations, all of which may cause inflammation, extracellular matrix remodeling, interstitial fibrosis, fibrofatty infiltration, and changes in the 3-dimensional cellular composition and architecture of the myocardium.1 Although cardiomyocytes make up the bulk of the tissue in the normal heart, nonmyocytes, specifically cardiac fibroblasts, can overwhelm the cardiac tissue during the initiation and progression of various cardiac diseases.2 Myocardial diseases can promote fibroblast differentiation into myofibroblasts, which are hypersecretory of extracellular matrix components.3 Hence, myofibroblasts are the primary mediators of wound healing in the damaged ventricle.4 They contribute to cardiac fibrosis and scar formation through their relatively greater ability to produce fibrillar and nonfibrillar collagens.5 They also contribute to extracellular matrix remodeling through their production of focal adhesion-associated proteins.6
See Article by Salvarani et al
Cardiac myofibroblasts interact with cardiomyocytes through cell surface proteins of the β-integrin and cadherin families.7 N-cadherin in particular has been shown to be involved in cardiomyocyte–myofibroblast interactions.8 Electrotonic coupling of neonatal cardiomyocytes and nonmyocytes in vitro was first demonstrated in the early 1970s.9 Subsequently, Rook et al10 showed that neonatal rat cardiac fibroblasts can connect with other fibroblasts and with cardiomyocytes through gap junctions with single channel conductance values of 21 pS and 32 pS, respectively. They also found in vitro evidence for connexin43 gap junctions between myocytes and fibroblasts.10 Gaudesius et al11 and Miragoli et al12 were first to demonstrate connexin43 and connexin45 expression both between fibroblasts and at fibroblast-to-cardiomyocyte junctions in cardiac strands.
Several years ago, we investigated the effects of cardiomyocyte–myofibroblast interactions …