In fibrosing hearts, myofibroblasts are associated with cardiac extracellular matrix remodeling. Expression of key genes in the transition of cardiac fibroblast to myofibroblast phenotype in post-myocardial infarction heart and in vitro has not been well addressed. Contractile, focal adhesion-associated, receptor proteins, fibroblast growth factor-2 (FGF-2) expression, and motility were compared to assess phenotype in adult and neonatal rat cardiac fibroblasts and myofibroblasts. Neonatal and adult fibroblasts undergo phenotypic transition to myofibroblastic cells, marked by increased a-smooth muscle actin (aSMA), smooth muscle myosin heavy chain (SMemb), extra domain-A (ED-A) fibronectin, paxillin, tensin, FGF-2, and TbRII receptor. Elevated ED-A fibronectin confirmed fibroblast to supermature myofibroblastic phenotype transition. Presence of myofibroblasts in vivo was noted in sections of healed infarct scar after myocardial infarction, and their expression is similar to that in culture. Thus, cultured neonatal and adult cardiac fibroblasts transition to myofibroblasts in vitro and share expression profiles of cardiac myofibroblasts in vivo. Reduced motility with in vitro passage reflects enhanced production of focal adhesions. Developmental Dynamics 239:1573-1584,

Ischemic heart disease is the most common cause of mortality worldwide. Cardiac fibroblasts and myofibroblasts, i.e., the hypersecretory, muscular, and contractile fibroblastic phenotype variant, play an important role in myocardial healing and are responsible for accumulation of collagen in the infarct scar as well as in viable myocardium. Thus, cardiac fibroblasts and myofibroblasts directly contribute to cardiac stiffness, altered performance, and ultimately to the onset of systolic and diastolic heart failure. Cardiotrophin-1 (CT-1) is a member of the IL-6 superfamily and is elevated in the serum of patients with ischemic heart disease and valvular heart disease; it is also known to induce cardiomyocyte hypertrophy in vitro. The recent, burgeoning awareness of the functions of IL-6 superfamily of cytokines within cardiovascular diseases predicates this summary of CT-1's effect in cardiac wound healing, and particularly after the induction of myocardial infarction. Further, we summarize recent results of cardiac CT-1 expression post-myocardial infarction (post-MI) as well as the effect of CT-1 on cultured primary adult rat cardiac fibroblasts with respect to proliferation and collagen secretion. It would appear that CT-1 plays an important and heretofore largely unrecognized role in infarct scar formation and angiogenesis in the rat model of chronic MI. Further work is required to determine factors that induce CT-1 expression, its interplay with other mediators of cardiac infarct wound healing in the setting of acute cardiac ischemia and chronic post-MI heart failure, and ultimately whether it confers a beneficial effect or contributes to maladaptive cardiac fibrosis.

LV, Dixon IM. Role of myosin light chain kinase in cardiotrophin-1-induced cardiac myofibroblast cell migration.

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