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Transmyocardial drilling revascularization combined with heparinized bFGF-incorporating stent activates resident cardiac stem cells via SDF-1/CXCR4 axis
Authors:Zhang Guang-Wei  Wen Ti  Gu Tian-Xiang  Li-Ling Jesse  Wang Chun  Zhao Ye  Liu Jing  Wang Ying  Liu Tian-Jun  Lü Feng
Affiliation:Department of Cardiac Surgery and Neurology, The First Hospital of China Medical University, Shenyang 110001, China.
Abstract:ObjectiveTo investigate whether transmyocardial drilling revascularization combined with heparinized basic fibroblast growth factor (bFGF)-incorporating degradable stent implantation (TMDRSI) can promote myocardial regeneration after acute myocardial infarction (AMI).MethodsA model of AMI was generated by ligating the mid-third of left anterior descending artery (LAD) of miniswine. After 6 h, the animals were divided into none-treatment (control) group (n = 6) and TMDRSI group (n = 6). For TMDRSI group, two channels with 3.5 mm in diameter were established by a self-made drill in the AMI region, into which a stent was implanted. Expression of stromal cell-derived factor-1α (SDF-1α) and CXC chemokine receptor 4 (CXCR4), cardiac stem cell (CSC)-mediated myocardial regeneration, myocardial apoptosis, myocardial viability, and cardiac function were assessed at various time-points.ResultsSix weeks after the operation, CSCs were found to have differentiated into cardiomyocytes to repair the infarcted myocardium, and all above indices showed much improvement in the TMDRSI group compared with the control group (P < 0.001).ConclusionsThe new method has shown to be capable of promoting CSCs proliferation and differentiation into cardiomyocytes through activating the SDF-1/CXCR4 axis, while inhibiting myocardial apoptosis, thereby enhancing myocardial regeneration following AMI and improving cardiac function. This may provide a new strategy for myocardial regeneration following AMI.
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