Journal Article

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

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

2025

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adipose Tissue - cytology / Adipose Tissue - metabolism / Air pollution / Angiogenesis / Animals / Apoptosis / Apoptosis - drug effects / Apoptosis Regulatory Proteins - genetics / Apoptosis Regulatory Proteins - metabolism / Bcl-2 protein / Biomedical and Life Sciences / Biomedical Engineering and Bioengineering / Body fat / Cardiomyocytes / Cardiovascular diseases / Cardiovascular system / Caspase-3 / Cell Biology / Cell Line / Conditioned medium from cultured adipose-derived stem cell (ADSC-CM) / Culture Media, Conditioned - pharmacology / Diet, High-Fat - adverse effects / Epidemiology / Fatty acids / Heart failure / High fat diet / High-fat diet (HFD) / Ischemia / Life Sciences / Male / Metabolism / Mice / Mice, Inbred C57BL / MicroRNAs / MicroRNAs - genetics / MicroRNAs - metabolism / miR221/222 / Mitochondria / Myocytes, Cardiac - cytology / Myocytes, Cardiac - drug effects / Myocytes, Cardiac - metabolism / Obesity / Obesity - metabolism / Oxidative stress / Palmitic acid / Palmitic acid (PA) / Paracrine signalling / Particulate matter / Particulate matter (PM) / Particulate Matter - adverse effects / Particulate Matter - toxicity / Reactive oxygen species / Reactive oxygen species (ROS) / Regenerative Medicine/Tissue Engineering / Risk factors / Stem Cells / Stem Cells - cytology / Stem Cells - metabolism / Transgenic mice