Ischemic heart disease (IHD) is the most occurring cardiovascular-associated disease, which is a primary leading cause of cardiac disability and death worldwide. Myocardial ischemia/reperfusion injury (MI/RI) has been linked to IHD-induced cardiomyocytes apoptosis and tissue damage. The clinical studies have indicated that pathophysiologic mechanisms of MI/RI are associated with reactive oxygen species generation, calcium overload, energy metabolism disorder, neutrophil infiltration, and others. However, the genetic mechanism of MI/RI remains unclear. In this study, we successfully established the reproducing abnormal heart observed in rat, of IHD-induced MI/RI post operation. By using these rats, we illustrated that expression of miR-181b-5p was increased not only in both hypoxia/reoxygenation-cultured H9C2 but also heart of myocardial ischemia/reperfusion (MI/R) rat.Suppression of the miR-181b-5p cardiomyocytes apoptosis and rescued myocardial infarction. Additionally, our data indicated that miR-181b-5p negatively regulates the expression of AKT3 and PIK3R3 through directly binding with its 3′-untranslated region. More importantly, suppression of miR-181b-5p protects the cardiomyocytes apoptosis and tissue damage from MI/R via regulation of PIK3R3 and AKT3. Hence, our study indicates that miR-181b-5p is essential for MI/RI via regulation of PI3K/Akt signaling pathway and could be a potential therapeutic target in IHD.
Atherosclerosis is a kind of chronic cardiovascular disease, characterized by oxidized low‐density lipoprotein (ox‐LDL) accumulation in macrophage. Tanshinone IIA (Tan), a lipophilic pharmacologically activate compound from Salvia miltiorrhiza Bunge, has been indicated to exert cardioprotective roles. Nevertheless, the biological role of Tan and regulatory mechanism in atherosclerosis are not fully established. In present study, atherosclerosis model was established in THP‐1‐derived macrophages by treatment of ox‐LDL. The adipogenesis was measured by Nile red staining. The expressions of inflammatory factors, microRNA‐130b (miR‐130b) and WNT5A were measured by quantitative real‐time polymerase chain reaction or Western blot. The target association between miR‐130b and WNT5A was explored via luciferase activity and RNA immunoprecipitation assay. The results showed that exposure of Tan inhibited ox‐LDL‐induced adipogenesis and expressions of interleukin‐1β (IL‐1β), IL‐6, and tumor necrosis factor‐alpha in THP‐1‐derived macrophages. miR‐130b expression was decreased in THP‐1‐derived macrophages treated by ox‐LDL and its overexpression attenuated adipogenesis as well as inflammatory response. miR‐130b knockdown reversed the regulatory effect of Tan on adipogenesis and inflammatory response in THP‐1‐derived macrophages stimulated by ox‐LDL. In addition, WNT5A acted as a functional target of miR‐130b and inhibited by Tan and miR‐130b. As a conclusion, Tan decreased the adipogenesis and inflammatory response by mediating miR‐130b and WNT5A, providing a novel theoretical foundation for treatment of atherosclerosis.
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