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BackgroundMyocardial infarction (MI) is often accompanied by cardiomyocyte apoptosis, which decreases heart function and leads to an increased risk of heart failure. The aim of this study was to examine the effects of transforming growth factor‐β receptor III (TGFβR3) on cardiomyocyte apoptosis during MI.Methods and ResultsAn MI mouse model was established by left anterior descending coronary artery ligation. Cell viability, apoptosis, TGFβR3, and mitogen‐activated protein kinase signaling were assessed by methylthiazolyldiphenyl‐tetrazolium bromide assay, terminal deoxynucleotidyl transferase‐mediated dUTP nick end labeling assay, immunofluorescence, electron microscopy, and Western blotting. Our results demonstrated that TGFβR3 expression in the border region of the heart was dynamically changed during MI. After stimulation with H2O2, TGFβR3 overexpression in cardiomyocytes led to increased cell apoptosis and activation of p38 signaling, whereas TGFβR3 knockdown had the opposite effect. ERK1/2 and JNK1/2 signaling was not altered by TGFβR3 modulation, and p38 inhibitor (SB203580) reduced the effect of TGFβR3 on apoptosis, suggesting that p38 has a nonredundant function in activating apoptosis. Consistent with the in vitro observations, cardiac TGFβR3 transgenic mice showed augmented cardiomyocyte apoptosis, enlarged infarct size, increased injury, and enhanced p38 signaling upon MI. Conversely, cardiac loss of function of TGFβR3 by adeno‐associated viral vector serotype 9–TGFβR3 short hairpin RNA attenuated the effects of MI in mice.Conclusions TGFβR3 promotes apoptosis of cardiomyocytes via a p38 pathway–associated mechanism, and loss of TGFβR3 reduces MI injury, which suggests that TGFβR3 may serve as a novel therapeutic target for MI.

The present study evaluated the effect of anagliptin on intimal hyperplasia following carotid artery injury in Sprague-Dawley rats. Sprague-Dawley rats weighing 280–300 g were injured using a 2F Fogarty balloon embolectomy catheter. The rats were divided into injury-(saline) and anagliptin-(10 mg/kg/day) treated groups. vascular injuries were induced in the left carotid artery, followed by evaluation of neointima formation at 28 days. The right and left carotid arteries were harvested and evaluated with histological evaluation, and the plasma activity of glucagon-like peptide 1 receptor (GLP-1), stromal cell-derived factor (SDF)-1α, interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-α were detected by ELISA analysis. Treatment with anagliptin decreased balloon injury-induced neointima formation, compared with the injury group (P<0.01). Body weight and food consumption did not alter following treatment with anagliptin. Anagliptin caused an increase in the serum active GLP-1 concentration, compared with the injury group. In addition, serum SDF-1α was significantly decreased by treatment with anagliptin (P<0.001). Anagliptin altered the serum activity of IL-6, IL-1β and TNF-α (P<0.01). The results of the present study demonstrated that anagliptin appeared to attenuate neointimal formation by inhibiting inflammatory cytokines and chemokines following balloon injury, and that treatment with a dipeptidyl peptidase 4 inhibitor may be useful for future preclinical studies and potentially for the inhibition of thrombosis formation following percutaneous coronary intervention.