Resveratrol Pretreatment Improved Heart Recovery Ability of Hyperglycemic Bone Marrow Stem Cells Transplantation in Diabetic Myocardial Infarction by Down-Regulating MicroRNA-34a

Abstract

AIM: To examine the effect of resveratrol (RSV) on bone marrow mesenchymal stem cells (BMSCs) under hyperglycemic conditions and on BMSCs transplantation in diabetic rats with myocardial infarction (MI).METHODS:In vitro, BMSCs were isolated from 3-week-old male Sprague Dawley (SD) rats and cultured under hyperglycemic conditions for up to 28 days. Cell viability was analyzed by cell counting kit-8 (CCK-8) assays. The expression of miR-34a was measured by RT-qPCR. Western blotting was used to examine the protein expression of SIRT1, P21, P16, VEGF and HIF-1α. A senescence-associated β-galactosidase assay was used to examine the senescence level of each group. In vivo, a diabetes model was established by feeding rats a high-sugar and high-fat diet for 8 weeks, injecting the animals with streptozotocin (STZ) and continuing high-sugar and high-fat feeding for 4 additional weeks. Then, left anterior descending coronary artery (LAD) cessation was used to established the myocardial infarction (MI) models. Each group of rats was transplanted with differentially preconditioned BMSCs after myocardial infarction. Ultrasound was used to analyze cardiac function 1 and 3 weeks after the operation, and frozen heart sections were used for immunohistochemical analysis, Masson staining and CD31 measurement. In addition, ELISA analysis of serum cytokine levels was performed.RESULTS: This study showed that the viability of BMSCs cultured under hyperglycemic conditions was decreased, the cells became senescent. Besides, an obviously increased in the expression of miR-34a was detected. Moreover, RSV preconditioning reduced the expression of miR-34a in BMSCs after high glucose stimulation and rejuvenated BMSCs under hyperglycemic conditions. Further analysis showed that the transplantation of RSV-BMSCs were benefit to heart recovery following infarction in diabetic rats, promoted proangiogenic factor release and increased arteriole and capillary densities.CONCLUSION: RSV rejuvenated BMSCs after chronic hyperglycemia-induced senescence by interacting with miR-34a and optimized the therapeutic effect of BMSCs on diabetes with myocardial infarction.

The Role of Stem Cells in the Treatment of Cardiovascular Diseases

“…In another study, resveratrol was found to induce SIRT1 expression in BM-MSCs by suppressing miR-34a. Transplantation of the pretreated cells into the areas of infarction enhanced the expression of the angiogenesis markers: VEGF and HIF-1α [181]. Similarly, pretreatment of aged MSCs with SRTT1720, another SIRT1 activator, significantly improved cardiac function after infarction in animal models.…”

“…Furthermore, heart tissues from the study group demonstrated lower capillary density and enhanced fibrosis [180]. In addition, pathological conditions may alter SIRT1 expression; for instance; high glucose reduces SIRT1 expression in BM-MSCs [181]. Agents that promote SIRT1 activity have been found to improve the treatment of cardiac conditions.…”

Association between the triglyceride glucose index and length of hospital stay in patients with heart failure and type 2 diabetes in the intensive care unit: a retrospective cohort study

“…Approximately 40% of HF patients are affected by DM, resulting in a two-to five-fold elevation in the risk of HF compared to normoglycemic individuals (42). Previous investigations emphasize the unfavorable clinical prognosis for diabetic patients with HF, displaying higher mortality rates than their normoglycemic counterparts (43)(44)(45). Despite the well-established association between diabetes and HF, there is limited data supporting the relationship between the TyG index and the LHS in patients with both HF and T2D.…”

MIR34A modulates lens epithelial cell apoptosis and cataract development via the HK1/caspase 3 signaling pathway

“…Increasing miRNAs have been identified to be aberrantly expressed in the process of disease development, and miRNAs are potential therapeutic targets for diseases, including cataracts [ 29 , 30 ]. Previous studies have shown that MIR34A is involved in various diseases, including myocardial infarction [ 31 ], senescence [ 32 ], tuberous sclerosis complex [ 33 ], and hepatocellular carcinoma [ 34 ]. Additionally, MIR34A is abnormally expressed in some age-related diseases, such as age-associated heart failure [ 35 ], atherosclerosis [ 36 ], and posterior capsule opacification [ 37 ].…”