Embryonic smooth muscle myosin heavy chain SMemb is expressed in pressure-overloaded cardiac fibroblasts

Left ventricular hypertrophy (LVH) is a secondary adaptation to increased e xternal load. Various qualitative and quantitative changes in myocytes and extracellular components occur during the development of LVH. It has recent ly been demonstrated that alpha-smooth muscle actin (alpha-SMA)-expressing myofibroblasts appear in the interstitium of the heart subjected to increas ed workload suggesting that cardiac fibroblasts as well as myocytes alter t heir phenotype in response to pressure overload. In the present study, to e xplore the load-induced response and phenotypic modulation of cardiac fibro blasts, the localization of embryonic smooth muscle myosin heavy chain (SMe mb) and alpha-SMA in thoracic aorta-constricted rat hearts was investigated by immunohistochemistry, and the morphology of the SMemb-expressing cells was examined by electron microscopy. In addition, to clarify the mechanisms by which SMemb is induced in pressure-overloaded hearts, mRNA expression o f SMemb in aorta-constricted rat hearts and in transforming growth factor-b eta 1 (TGF-beta 1)-treated or mechanically-stretched cultured cardiac fibro blasts was investigated. Enhanced staining of SMemb and alpha-SMA was detec ted in the interstitial spindle-shaped cells in the fibrotic lesions of the pressure-overloaded left ventricles by immunohistochemistry. These cells w ere demonstrated by electron microscopy to have features specific for activ ated fibroblasts such as serrated nuclei or prominent rough endoplasmic ret iculum. These cells also had characteristic features of myofibroblasts, i.e . irregularly arranged actin filaments and scattered dense bodies. Northern blot analysis revealed increased mRNA levels of SMemb both in aorta-constr icted rat hearts and in cultured cardiac fibroblasts stimulated by TGF-beta 1 or by mechanical stretch. These results suggest that SMemb may be a mole cular marker both for the detection of activated cardiac fibroblasts that m ay play important roles in the remodeling of pressure-overloaded cardiac in terstitium, and for the identification of the regulatory mechanisms that co ntrol the phenotypic modulation of cardiac fibroblasts in response to press ure overload.