Adipose-derived mesenchymal stem cells (ADMSCs) protect against hyperglycemia and hyperlipidemia-induced heart failure by inhibiting autophagy-related apoptosis

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Abstract Background Mesenchymal stem cells (MSCs), a type of seed cell, are expected to improve impaired diabetic cardiac function. Inflammation and autophagy play an important role in the development of metabolic disorder-induced heart failure. The aim of this work was to assess the effect of adipose-derived mesenchymal stem cells (ADMSCs) on metabolic disorder-induced heart failure and the underlying mechanisms. Methods Eight weeks old male C57BL/6 mice were randomly divided into three groups: normal chow mice (NC group), high-fat diet-fed and streptozotocin-treated mice (HFD+STZ group) and mice administered with ADMSCs-once per week for 3 months after the mice were treated with HFD+STZ (ADMSCs+HFD+STZ group). Once a week lipid and glucose levels were measured and echocardiography was performed. Immunohistochemistry was used to detect the adhesion of macrophages in heart tissue in all three groups. Inflammatory cytokines such as interleukin-1β (IL-1β), tumor necrosis factor α (TNFα), interleukin-6 (IL-6) and interleukin-8 (CXCL-15) were measured by western blot or RT-qPCR. In vitro, H9c2 cardiomyocytes were stimulated by 33mM glucose in the presence or absence of IL-1β. Transmission electron microscopy, mRFG-GFP-LC3 assays and flow cytometry were used to investigate autophagy-related apoptosis in H9c2 cells. Results HFD+STZ treated mice presented significant cardiac hypertrophy, body weight loss, hyperglycemia and hyperlipidemia. However, these changes were remarkably reversed by the administration of ADMSCs. The administration of ADMSCs also remits histological alterations and deposition of collagen in the heart tissue. Furthermore, ADMSCs downregulated the adhesion of macrophages in heart tissue. More importantly, IL-1β from macrophages increased the autophagy of myocardial cells stimulated with high glucose, which eventually led to apoptosis and cardiac dysfunction. Conclusions This study confirmed that ADMSCs may have potential for use in improving cardiac function by restraining autophagy and apoptosis of myocardial cells. We also identified the roles of the IL-1β in hyperglycemia- and hyperlipidemia-induced cardiac injuries, which may be a key factor for diabetic complications.

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