Fibronectin and collagen types I and III are the major components of the interstitial fibrillar network; thus, it has been hypothesized that the up-regulation of fibroblasts genes encoding these components accounts, in part, for the increase in fibrosis observed during the transition to heart failure and contributes to the decline in contractile performance. The elaboration of the extracellular matrix by fibroblasts is influenced by TGF-b1 and plays an important role in pressure-overload Diphemanil Methylsulfate cardiac hypertrophy. The cytokine TGF-b1 is expressed by and modulates myocytes, vascular cells and fibroblasts; its expression rises in myocardium in experimental and human heart disease, and it promotes hypertrophy, fibrosis, apoptosis, and endothelial-mesenchymal transition. Furthermore, a generalized increase in the level of contractile proteins, such as b-MHC and myofibroblast Butenafine hydrochloride marker alpha smooth muscle actin, constitutes a marker of cardiac hypertrophy. Shifts from the normally predominant aMHC toward b-MHC are often observed in cardiomyocytes from hypertrophied and failing hearts. a-SMA is expressed in cardiomyocytes during early stages of heart development and in dedifferentiated cardiac fibroblasts and its reactivation is considered a potential marker of ventricular hypertrophy. Finally, the BNP serum level is also considered to be one of several criteria indicating the initiation of a pathological response in hypertrophied failing hearts. Cardiac and circulating pro-inflammatory markers such as CRP, interleukins and TNF-a have been also associated with cardiac disease. Severe hypothyroidism caused dilated cardiomyopathy with decreased a-MHC and increased b-MHC, phospholamban and ANP, an accepted clinical marker of the diseased hypertrophic heart. After thyroid hormone replacement the alterations in gene expression were reversed with overall improvement in myocardial performance. In keeping, thyroid replacement therapy has been used by many investigators to treat patients with heart failure. However, the beneficial therapeutic effects obtained in the short term might be followed by pathological manifestations of the systemic effects of thyroid hormones during longer treatments.