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Mast Cell Granule Could Regulates Left Ventricular Function after Myocardial Infarction through Balancing between Apoptosis and Angiogenesis
전남대학교병원 심장센터, 전남대학교 심혈관질환 치료재생 특성화사업단, 과학기술부 제대혈 및 중간엽줄기세포 기능연구사업단
권진숙, 김용숙, 홍문화, 조애신, 신선미, 김계훈, 박형욱, 홍영준, 김주한, 정명호, 조정관, 박종춘, 강정채, 안영근
Background: Mast cells are multifunctional cells containing various mediators such as cytokines, proteases, and histamine. They are found in most parts of the human body, including heart and vessels and implicated in ventricular hypertrophy, heart failure, and myocardial infarction. Mast cells has a various effects on the progression of myocardial infarction at different concentration. Methods: We evaluated the effects of MCG at different concentrations on various cell types such as cardiomyocytes (CMs), bone marrow cells (BMCs), human endothelial progenitor cells (hEPCs), and human umbilical cord vein endothelial cells (hUVECs). CMs and BMCs were incubated with mast cell granules (MCGs) [low dose: 1% or high dose: 10% of original dose (3.75x105/ml)] for 24 hours. Using hEPCs and hUVECs, we evaluated the angiogenic effects of tubular formation and migration. To evaluate the effects of MCGs on myocardial infarction rat model (left anterior descending coronary artery occlusion for 1 hour and reperfusion), we injected immediately MCGs (low dose: 2μl/100μl or high dose; 20μl/100μl) at peri-infarct area. Results: MCGs increased apoptosis of CMs and BMCs at high dose under serum starvation condition, but MCGs at low dose, do not increased apoptosis on CMs and interestingly, increased survival of BMCs (control group: 68.0±4.9% vs. MCGs treated group: 83.5±8.5%, p<0.05). The increased expression of stem cell factor and interleukin-6 by RT-PCR and phosphorylated Akt by Western blot were observed in the low dose MCGs treated cells. In Boyden chamber assay, low dose MCGs increased migration of hEPCs (7.6±4.9% vs. 18.1±3.0%, p<0.01) and hUVECs (1.0±0.2% vs. 14.5±7.6%, p<0.01). In MCGs at low dose treated rats, improved left ventricular function and increased capillary density 3 times more than the control rats were observed in peri-infarct area. Conclusion: Mast cells at low dose has a beneficial effects on the progression after acute myocardial infarction.


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