Elevated levels of active myocardial TGF-beta1 induced overt fibrosis in the atria but inhibited ventricular fibroblast DNA synthesis and delayed wound healing in the adult mouse ventricle.
Increased TGF-beta(1) activity by itself is sufficient to cause atrial fibrosis but insufficient to promote ventricular fibrosis in the adult mouse ventricle.
Increased transforming growth factor (TGF)-beta(1) activity has been observed during pathologic cardiac remodeling in a variety of animal models. In an effort to establish a causal role of TGF-beta(1) in this process, transgenic mice with elevated levels of active myocardial TGF-beta(1) were generated. The cardiac-restricted alpha-myosin heavy chain promoter was used to target expression of a mutant TGF-beta(1) cDNA harboring a cysteine-to-serine substitution at amino acid residue 33. This alteration blocks covalent tethering of the TGF-beta(1) latent complex to the extracellular matrix, thereby rendering a large proportion (>60%) of the transgene-encoded TGF-beta(1) constitutively active. Although similar levels of active TGF-beta(1) were present in the transgenic atria and ventricles, overt fibrosis was observed only in the atria. Surprisingly, increased active TGF-beta(1) levels inhibited ventricular fibroblast DNA synthesis in uninjured hearts and delayed wound healing after myocardial injury. These data suggest that increased TGF-beta(1) activity by itself is insufficient to promote ventricular fibrosis in the adult mouse ventricle.
Nakajima et al. (Fri,) conducted a other in Cardiac remodeling and fibrosis. Mutant TGF-beta1 transgene expression was evaluated on Cardiac fibrosis, ventricular fibroblast DNA synthesis, and wound healing. Elevated levels of active myocardial TGF-beta1 induced overt fibrosis in the atria but inhibited ventricular fibroblast DNA synthesis and delayed wound healing in the adult mouse ventricle.