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Previous studies have established that proteinase- activated receptor 2 (PAR2) activation protects against myocardial ischemia/reperfusion injury (MI/RI). However, the role of PAR2 deficiency in MI/RI remains unclear. The aim of the present study was to examine the effect of PAR2 deficiency on cardiomyocyte apoptosis and to clarify the potential molecular mechanisms for its protective effect against MI/RI. Using a mouse model of MI/RI, cardiac function was evaluated by echocardiography, infarct size was assessed by triphenyltetrazolium chloride staining, and myocardial cell apoptosis was measured by terminal deoxynucleotide transferase-mediated dUTP nick end-labeling staining. Annexin V/propidium iodide staining, and expression of Bcl-2 and cleaved PARP were determined to assess apoptosis in myocardial H9c2 cells exposed to hypoxia/reoxygenation (H/R) injury-simulating MI/RI. Phosphorylated ERK1/2, JNK, and p38 MAPK protein expression levels were analyzed by western blotting. The findings indicated that PAR2 deficiency markedly reduced cardiomyocyte apoptosis in the MI/RI mouse model, as well as in myocardial H9c2 cells exposed to H/R. Furthermore, PAR2 knockdown clearly prevented phosphorylation of ERK1/2 and JNK in myocardial H9c2 cells. The results revealed that PAR2 deficiency alleviated MI/RI-associated apoptosis by inhibiting phosphorylation of ERK1/2 and JNK. Therefore, targeted PAR2 silencing may be a potential therapeutic approach for alleviation of MI/RI. [ABSTRACT FROM AUTHOR]

Electrospinning using biocompatible polymer scaffolds, seeded with or without stem cells, is considered a promising technique for producing fibrous scaffolds with therapeutic possibilities for ischemic heart disease. However, no optimal scaffolds for treating ischemic heart disease have been identified thus far. In the present study, it was evaluated whether electrospun silk fibroin (SF)-blended poly(L-lactic acid-co-ε-caprolactone) [P(LLA-CL)] scaffolds that were seeded with cluster of differentiation 117 (c-kit)+ bone marrow (BM) cells may serve a protective role in cardiac remodeling following myocardial infarction (MI). Mechanical characteristics and cytocompatibility were compared between SF/P(LLA-CL) and P(LLA-CL) electrospun nanofibrous scaffolds in vitro. It was observed that MI led to a significant increase of the c-kit+ BM cell subpopulation in mice. Magnetic activated cell sorting was performed to harvest the c-kit+ cell population from the BM of mice following MI. c-kit+ BM cells were seeded on SF/P(LLA-CL) and P(LLA-CL) electrospun nanofibrous scaffolds. Results indicated that SF/P(LLA-CL) electrospun nanofibrous scaffolds were superior to P(LLA-CL) electrospun nanofibrous scaffolds in improving c-kit+ BM cell proliferation. Additionally, compared with pure SF/P(LLA-CL) electrospun nanofibrous scaffolds, SF/P(LLA-CL) scaffolds seeded with c-kit+ BM cells resulted in lower levels of MI markers and reduced infarct size, leading to greater global heart function improvement in vivo. The findings of the present study indicated that SF/P(LLA-CL) electrospun nanofibrous scaffolds seeded with c-kit+ BM cells exert a protective effect against MI and may be a promising approach for cardiac regeneration after ischemic heart disease. [ABSTRACT FROM AUTHOR]