脂肪来源干细胞条件培养基中的MiR221/222可减轻颗粒物和高脂饮食诱导的心脏细胞凋亡。

MiR221/222 in the conditioned medium of adipose-derived stem cells attenuates particulate matter and high-fat diet-induced cardiac apoptosis.

作者信息

Chen Ya-Chun, Pu Chi-Ming, Lin Shu-Rung, Lin Shu-Wha, Yu I-Shing, Shih Ho-Jun, Lee Chiang-Wen, Lee Ming-Hsueh, Kuo Yen-Ting, Chen Yuh-Lien

机构信息

Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, No. 1, Sec 1, Ren-Ai Road, Taipei, 10051, Taiwan, ROC.

Division of Plastic Surgery, Department of Surgery, Cathay General Hospital, Taipei, Taiwan, ROC.

出版信息

Stem Cell Res Ther. 2025 Jun 3;16(1):285. doi: 10.1186/s13287-025-04381-8.

DOI:10.1186/s13287-025-04381-8

PMID:40462170

Abstract

BACKGROUND

Air pollution and obesity are crucial risk factors for cardiovascular disease (CVD), with epidemiological evidence indicating that air pollution exacerbates obesity-induced cardiac damage. Treatment with adipose-derived stem cells (ADSCs) attenuates cardiac damage by releasing paracrine factors. However, the effects of ADSCs on air pollution- and obesity-induced cardiomyocyte apoptosis and the related mechanisms are still unclear.

METHODS

Palmitic acid (PA) and a high-fat diet (HFD) were used to cause obesity, and particulate matter (PM) was used to simulate air pollution in the study. We studied the impact of conditioned medium from adipose-derived stem cells (ADSC-CM) on the apoptosis of PA + PM-treated H9c2 cells and HFD + PM-treated mouse cardiomyocytes and the underlying mechanisms involved.

RESULTS

The levels of apoptosis-related proteins (PUMA and cleaved caspase-3) were significantly increased in PA + PM-treated H9c2 cells and HFD + PM-treated mouse cardiomyocytes, whereas the antiapoptotic protein Bcl-2 expression was reduced. However, ADSC-CM treatment effectively reduced the PUMA and cleaved caspase-3 expression but increased the Bcl-2 expression. ADSC-CM significantly reduced PA + PM- and HFD + PM-induced cardiomyocyte apoptosis, as detected by the TUNEL assay. RT-qPCR revealed that PA + PM and HFD + PM significantly reduced miR221/222 levels, whereas ADSC-CM treatment increased miR221/222 levels. Furthermore, knockout (KO) and transgenic (TG) mice were used to demonstrate that miR221/222 in ADSC-CM ameliorated cardiac apoptosis that was induced by HFD + PM treatment. Furthermore, PA + PM treatment increased the reactive oxygen species (ROS) production, which triggered mitochondrial fission and contributed to apoptosis. However, ADSC-CM effectively reduced ROS levels and regulated mitochondrial fission, alleviating cellular apoptosis.

CONCLUSIONS

Our findings demonstrated that ADSC-CM attenuated PA + PM-induced cardiomyocyte apoptosis by modulating miR221/222 levels and suppressing ROS production.

摘要

背景

空气污染和肥胖是心血管疾病（CVD）的关键危险因素，流行病学证据表明空气污染会加剧肥胖引起的心脏损伤。脂肪来源干细胞（ADSCs）治疗通过释放旁分泌因子减轻心脏损伤。然而，ADSCs对空气污染和肥胖诱导的心肌细胞凋亡的影响及其相关机制仍不清楚。

方法

在本研究中，使用棕榈酸（PA）和高脂饮食（HFD）诱导肥胖，并使用颗粒物（PM）模拟空气污染。我们研究了脂肪来源干细胞条件培养基（ADSC-CM）对PA + PM处理的H9c2细胞和HFD + PM处理的小鼠心肌细胞凋亡的影响及其潜在机制。

结果

PA + PM处理的H9c2细胞和HFD + PM处理的小鼠心肌细胞中，凋亡相关蛋白（PUMA和裂解的caspase-3）水平显著升高，而抗凋亡蛋白Bcl-2表达降低。然而，ADSC-CM处理有效降低了PUMA和裂解的caspase-3表达，但增加了Bcl-2表达。通过TUNEL检测发现，ADSC-CM显著减少了PA + PM和HFD + PM诱导的心肌细胞凋亡。RT-qPCR显示，PA + PM和HFD + PM显著降低了miR221/222水平，而ADSC-CM处理则增加了miR221/222水平。此外，使用基因敲除（KO）和转基因（TG）小鼠证明，ADSC-CM中的miR221/222改善了HFD + PM处理诱导的心脏凋亡。此外，PA + PM处理增加了活性氧（ROS）的产生，引发线粒体分裂并导致细胞凋亡。然而，ADSC-CM有效降低了ROS水平并调节线粒体分裂，减轻了细胞凋亡。