MiR221/222 in the conditioned medium of adipose-derived stem cells attenuates particulate matter and high-fat diet-induced cardiac apoptosis
Journal
Stem Cell Research and Therapy
Journal Volume
16
Journal Issue
1
Start Page
285
ISSN
1757-6512
Date Issued
2025-06-03
Author(s)
Chen, Ya-Chun
Pu, Chi-Ming
Lin, Shu-Rung
Yu, I-Shing
Shih, Ho-Jun
Lee, Chiang-Wen
Lee, Ming-Hsueh
Kuo, Yen-Ting
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.
Publisher
BioMed Central Ltd
Type
journal article