Mineralocorticoid receptor deficiency improves the therapeutic effects of mesenchymal stem cells for myocardial infarction via enhanced cell survival

• Published in: Journal of cellular and molecular medicine 2019-02, Vol.23 (2), p.1246-1256
• Main Authors: Xie, Xinxing, Shen, Yunli, Chen, Jing, Huang, Zheyong, Ge, Junbo
• Format: Article
• Language: English
• Subjects: Adenoviridae; Animals; Annexin V; Apoptosis; Bone marrow; Cardiovascular diseases; Cell Survival; Cells, Cultured; Coronary artery disease; Depletion; Heart attacks; Heart diseases; Hypoxia; Infarction; Male; Mesenchymal Stem Cell Transplantation - methods; Mesenchymal stem cells; Mesenchymal Stem Cells - cytology; Mesenchyme; mineralocorticoid receptor; Myocardial infarction; Myocardial Infarction - metabolism; Myocardial Infarction - pathology; Myocardial Infarction - therapy; Myocardium; Original; Rats; Rats, Sprague-Dawley; Reactive oxygen species; Receptors, Mineralocorticoid - deficiency; siRNA; Stem cell transplantation; Stem cells; Vascular endothelial growth factor
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.14026

The poor survival of stem cells seriously limits their therapeutic efficacy for myocardial infarction (MI). Mineralocorticoid receptor (MR) activation plays an important role in the pathogenesis of multiple cardiovascular diseases. Here, we examined whether MR silencing in bone marrow derived mesenchymal stem cells (MSCs) could improve MSCs’ survival and enhance their cardioprotective effects in MI. MSCs from male Sprague‐Dawley rats were transfected with adenoviral small interfering RNA to silence MR (siRNA‐MR). MR silencing decreased hypoxia‐induced MSCs’ apoptosis, as demonstrated by Annexin V/7‐AAD staining. The mechanisms contributing to the beneficial effects of MR depletion were associated with inhibiting intracellular reactive oxygen species production and increased Bcl‐2/Bax ratio. In vivo study, 1 × 106 of MSCs with or without siRNA‐MR were injected into rat hearts immediately after MI. Depletion of MR could improve the MSCs’ survival significantly in infarcted myocardium, associated with more cardiac function improvement and smaller infarct size. Capillary density were also significantly higher in siRNA group with increased expression of vascular endothelial growth factor. Our study demonstrated that silencing MR promoted MSCs’ survival and repair efficacy in ischaemic hearts. MR might be a potential target for enhancing the efficacy of cell therapy in ischaemic heart disease.