Qiliqiangxin attenuates hypoxia‐induced injury in primary rat cardiac microvascular endothelial cells via promoting HIF‐1α‐dependent glycolysis

Abstract

Protection of cardiac microvascular endothelial cells (CMECs) against hypoxia injury is an important therapeutic strategy for treating ischaemic cardiovascular disease. In this study, we investigated the effects of qiliqiangxin (QL) on primary rat CMECs exposed to hypoxia and the underlying mechanisms. Rat CMECs were successfully isolated and passaged to the second generation. CMECs that were pre‐treated with QL (0.5 mg/mL) and/or HIF‐1α siRNA were cultured in a three‐gas hypoxic incubator chamber (5% CO2, 1% O2, 94% N2) for 12 hours. Firstly, we demonstrated that compared with hypoxia group, QL effectively promoted the proliferation while attenuated the apoptosis, improved mitochondrial function and reduced ROS generation in hypoxic CMECs in a HIF‐1α‐dependent manner. Meanwhile, QL also promoted angiogenesis of CMECs via HIF‐1α/VEGF signalling pathway. Moreover, QL improved glucose utilization and metabolism and increased ATP production by up‐regulating HIF‐1α and a series of glycolysis‐relevant enzymes, including glucose transport 1 (GLUT1), hexokinase 2 (HK2), 6‐phosphofructokinase 1 (PFK1), pyruvate kinase M2 (PKM2) and lactate dehydrogenase A (LDHA). Our findings indicate that QL can protect CMECs against hypoxia injury via promoting glycolysis in a HIF‐1α‐dependent manner. Lastly, the results suggested that QL‐dependent enhancement of HIF‐1α protein expression in hypoxic CMECs was associated with the regulation of AMPK/mTOR/HIF‐1α pathway, and we speculated that QL also improved HIF‐1α stabilization through down‐regulating prolyl hydroxylases 3 (PHD3) expression.

Qiliqiangxin reduced cardiomyocytes apotosis and improved heart function in infarcted heart through Pink1/Parkin -mediated mitochondrial autophagy

“…It has exhibited remarkable curative effect in clinical applications and holds the traditional functions of strengthening heart, diuresis and vasodilation [17,19,20,24]. Basic research shows that QLQX could restrain hypoxia-induced injury in primary rat cardiac microvascular endothelial cells via promoting glycolysis in a HIF-1a-dependent manner [27]. During hypoxia, cardiac microvascular endothelial cells (CMVECs) promote the expression of vascular endothelial growth factor (VEGF) and QLQX could attenuate this injury via facilitating hypoxia inducible factor-1α(HIF-1α)dependent glycolysis [28].…”

Qiliqiangxin Capsules Optimize Cardiac Metabolism Flexibility in Rats With Heart Failure After Myocardial Infarction

“…QLQX has been proven to have a great potential as a promising metabolic modulator as it can regulate cardiac glucose and FA metabolism simultaneously by upregulating a large number of enzymes, including GLUT4, GLUT1, CD36, and so forth in different pathological models (Shen et al, 2017;Wang et al, 2017Wang et al, , 2018. This multi-targeting regulation might depend on the multiple components identified in QLQX, encompassing ginsenoside Rb1, astragaloside, salvianolic acid A, and so forth (Zhang et al, 2019).…”

Dexmedetomidine alleviated neuropathic pain in dorsal root ganglion neurons by inhibition of anaerobic glycolysis activity and enhancement of ROS tolerance

“…Pyruvate dehydrogenase 1 (PDK1) is an essential enzyme for pyruvate dehydrogenation by the mitochondria [49]. In addition, several enzymes involved in glycolysis were found to be elevated, such as pyruvate kinase 2 (PK2), phosphofructokinase 1 (PFK1) and hexokinase 2 (HK2), in disease [50]. In our study, we also demonstrated that dexmedetomidine markedly decreased NADPHase, HK2, PFK1, PK2, Glut1, LDHA and PDK1 expression, which were induced by H 2 O 2, in rat DRG neurons.…”