No abstract

␤-Catenin is a transcriptional regulator of several genes involved in survival and proliferation. Although previous studies suggest that ␤-catenin may be involved in the process of preconditioning and healing after myocardial infarction (MI), little is known regarding the role of ␤-catenin in cardiomyocytes and cardiac fibroblasts. We investigated the role of ␤-catenin in cardiomyocytes and cardiac fibroblasts and whether ␤-catenin overexpression could reduce MI size. Adenovirus-mediated gene transfer of nonphosphorylatable constitutively active ␤-catenin (Ad-catenin) decreased apoptosis in cardiomyocytes and cardiac fibroblasts with increased expression of survivin and Bcl-2. Although Ad-catenin increased the percentage of cells in the S phase with enhanced expression of cyclin D1 and E2 in both cell types, the increase in cell number was only evident in cardiac fibroblasts, whereas hypertrophy and binuclear cells were more prominent in cardiomyocytes. All of these effects of ␤-catenin gene transfer were blocked by inhibition of its nuclear translocation. Furthermore, Ad-catenin enhanced the expression of vascular endothelial growth factor in both cells and induced differentiation of cardiac fibroblasts into myofibroblasts. In a rat MI model, injection of Ad-catenin into the infarct border zone resulted in a significantly decreased MI size with anti-apoptotic effect and cell cycle activation in both cardiomyocytes and myofibroblasts. ␤-Catenin may play an important role in the healing process after MI by promoting survival and cell cycle not only in cardiomyocytes but also in cardiac fibroblasts with its differentiation into myofibroblasts.␤-Catenin is known to have dual functions. Membranebound ␤-catenin maintains tissue architecture and cell polarity at adherens junctions by linking the cadherin cytoplasmic tail to the actin cytoskeleton (1). Cytoplasmic ␤-catenin translocates into the nucleus where it forms a complex with transcription factors of Tcf/Lef family and activates the expression of specific genes involved in cell survival and proliferation (1, 2). Glycogen-synthase kinase 3␤ (GSK3␤) 3 constitutively phosphorylates cytoplasmic ␤-catenin resulting in proteosomal degradation (3), and Wnt signaling inhibits GSK3␤, leading to cytoplasmic accumulation of ␤-catenin (4).Although the critical roles of ␤-catenin during development (5) and in neoplastic disease have been well described previously (6), relatively little is known about the role of ␤-catenin in cardiomyocytes and cardiac fibroblasts, which are not only the principal cells comprising the myocardium but also key cells involved in remodeling after myocardial infarction (MI). Recent studies have suggested that ␤-catenin is capable of regulating survival/apoptosis and hypertrophy of cardiomyocytes (7,8). The inactivation of GSK3␤ by statins has been shown to inhibit cardiomyocyte apoptosis (7), whereas activated GSK3␤ was shown to attenuate cardiac hypertrophy in vivo (8). In addition, Wnt/␤-catenin pathways have also been implicated in fibroblast p...

Despite the greater reduction of platelet reactivity by addition of cilostazol to conventional DAT, TAT did not show superiority in reducing the composite of adverse cardiovascular outcomes after DES implantation. (The Efficacy of CILostazol ON Ischemic Complications After DES Implantation [CILON-T]; NCT00776828).

Background-Ischemic