Retracted: Tetramethylpyrazine partially relieves hypoxia‐caused damage of cardiomyocytes H9c2 by downregulation of miR‐449a

Abstract

Inadequate oxygen supply is probably one of the most important pathophysiological mechanisms of cardiomyocyte damage in ischemic heart disease. Tetramethylpyrazine (TMP, also known as ligustrazine) is the main active ingredient isolated from the rhizome of Ligusticum chuanxiong Hort. A previous study reported that the TMP could exert cardioprotective activity. This study aimed to explore the molecular mechanism of the protective effects of TMP on cardiomyocyte damage caused by hypoxia. The viability and apoptosis of cardiomyocytes H9c2 were detected using cell counting kit‐8 assay and annexin V‐FITC/PI staining, respectively. Quantitative reverse transcription polymerase chain reaction was conducted to measure the expression level of microRNA‐449a (miR‐449a). Cell transfection was performed to upregulate the expression level of miR‐449a or downregulate the expression level of sirtuin 1 (Sirt1). The protein expression levels of Sirt1 and key factors involved in cell apoptosis and phosphatidylinositol 3‐kinase/protein kinase 3 (PI3K/AKT) pathway were evaluated using western blot analysis. We found that the hypoxia incubation inhibited H9c2 viability, induced cell apoptosis, and inactivated the PI3K/AKT pathway. TMP treatment partially relieved the hypoxia‐caused H9c2 cell viability loss and apoptosis, as well as reversed the hypoxia‐caused inactivation of the PI3K/AKT pathway. Moreover, TMP partially alleviated the upregulation of miR‐449a in H9c2 cells caused by hypoxia. Overexpression of miR‐449a weakened the effects of TMP on hypoxia‐treated H9c2 cells. Furthermore, Sirt1 was a target gene of miR‐449a. Knockdown of Sirt1 also weakened the effects of TMP on hypoxia‐treated H9c2 cells. In conclusion, TMP partially relieved hypoxia‐caused cardiomyocytes H9c2 viability loss and apoptosis at least through downregulating miR‐499a, upregulating Sirt1, and then activating the PI3K/AKT pathway.

Circular RNA circ‐Ttc3 protects HaCaT cells from hypoxic injury by downregulation of miR‐449a

“…MiR-449a downregulation declined viability, p/t-PI3K and p/t-AKT as well as raised apoptosis and cleaved-Caspase-3 expression in H9c2 cells. 38 Consistent with the study, upregulating miR-449a expression raised apoptosis and expression of p53, cleaved-Caspase-3 and cleaved-Caspase-9, which implied that hypoxic injury was relieved by miR-449a downregulation.…”

“…However, the impact of miR‐449a in hypoxic‐treated cells has been greatly limited. And existing evidence of miR‐449a focus on myocardial diseases in cardiomyocytes . Zhang et al reported that tetramethylpyrazine attenuated hypoxic injury in a certain degree via downregulating miR‐449a through PI3K/AKT pathway in H9c2 cells.…”

“…PI3K/AKT pathway has been elucidated to play a critical part in proliferation and viability, and activation of PI3K/AKT pathway represses apoptosis and raises viability . It is widely appraised that PI3K/AKT pathway acted as a critical role in improving survival, especially in hypoxia condition . In addition, NF‐κB acts as a vital factor in regulating genes that regulate apoptosis, growth, and inflammatory responses .…”

“…4 It is widely appraised that PI3K/AKT pathway acted as a critical role in improving survival, especially in hypoxia condition. 38 In addition, NF-κB acts as a vital factor in regulating genes that regulate apoptosis, growth, and inflammatory responses. 42 NF-κB also affects cell survival and induces proapoptotic and antiapoptotic genes based on cell types and stimulations.…”

Antiarrhythmic Mechanisms of Chinese Herbal Medicine Dingji Fumai Decoction

“…In addition, with the development of mass spectrometry, multiple constituents of the components of DFD have been analyzed and characterized in recent years [29][30][31][32][33][34]. Modern pharmacological studies have shown that the components of DFD have anti-inflammatory [35][36][37][38][39], antioxidative stress [40][41][42], and myocardial protection [42][43][44][45] effects. Inflammation and oxidative stress are closely related to arrhythmia [46][47][48].…”