Popov Sergey V, Maslov Leonid N, Mukhomedzyanov Alexandr V, Kurbatov Boris K, Gorbunov Alexandr S, Kilin Michail, Azev Viacheslav N, Khlestkina Maria S, Sufianova Galina Z
Tomsk National Research Medical Center, Cardiology Research Institute, The Russian Academy of Sciences, Kyevskaya 111A, Tomsk 634012, Russia.
Branch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, The Russian Academy of Sciences, Pushchino 142290, Russia.
Pharmaceutics. 2023 Mar 22;15(3):1029. doi: 10.3390/pharmaceutics15031029.
In-hospital mortality in patients with ST-segment elevation myocardial infarction (STEMI) is 5-6%. Consequently, it is necessary to develop fundamentally novel drugs capable of reducing mortality in patients with acute myocardial infarction. Apelins could be the prototype for such drugs. Chronic administration of apelins mitigates adverse myocardial remodeling in animals with myocardial infarction or pressure overload. The cardioprotective effect of apelins is accompanied by blockage of the MPT pore, GSK-3β, and the activation of PI3-kinase, Akt, ERK1/2, NO-synthase, superoxide dismutase, glutathione peroxidase, matrix metalloproteinase, the epidermal growth factor receptor, Src kinase, the mitoK channel, guanylyl cyclase, phospholipase C, protein kinase C, the Na/H exchanger, and the Na/Ca exchanger. The cardioprotective effect of apelins is associated with the inhibition of apoptosis and ferroptosis. Apelins stimulate the autophagy of cardiomyocytes. Synthetic apelin analogues are prospective compounds for the development of novel cardioprotective drugs.
ST段抬高型心肌梗死(STEMI)患者的院内死亡率为5%-6%。因此,有必要研发出能够降低急性心肌梗死患者死亡率的全新药物。Apelin可能成为这类药物的原型。长期给予Apelin可减轻心肌梗死或压力超负荷动物的不良心肌重塑。Apelin的心脏保护作用伴随着线粒体通透性转换孔(MPT孔)、糖原合成酶激酶-3β(GSK-3β)的阻断,以及磷脂酰肌醇-3激酶(PI3-激酶)、蛋白激酶B(Akt)、细胞外信号调节激酶1/2(ERK1/2)、一氧化氮合酶、超氧化物歧化酶、谷胱甘肽过氧化物酶、基质金属蛋白酶、表皮生长因子受体、Src激酶、线粒体钾通道、鸟苷酸环化酶、磷脂酶C、蛋白激酶C、钠/氢交换体和钠/钙交换体的激活。Apelin的心脏保护作用与细胞凋亡和铁死亡受抑制有关。Apelin可刺激心肌细胞的自噬。合成的Apelin类似物是开发新型心脏保护药物的有前景的化合物。