心力衰竭的发生、发展涉及血管内皮功能障碍、炎症和氧化应激,这一病理生理过程会影响一氧化氮(nitric oxide,NO)-可溶性鸟苷酸环化酶(soluble guanylate cyclase,sGC)-环磷酸鸟苷-(cyclic guanosine monophosphate,cGMP)信号通路活性.维利西呱可通过刺激sGC提高cGMP水平,cGMP作为第二信使激活蛋白激酶、磷酸二酯酶和下游的信号通路,不仅舒张血管,改善冠状动脉血流量,而且可抑制炎症、心肌纤维化的进展,从而改善心衰患者的预后.目前维利西呱在射血分数降低的心力衰竭(heart failure with reduced ejection fraction,HFrEF)和射血分数保留的心力衰竭(heart failure with preserved ejection fraction,HFpEF)中均进行数个临床研究,其治疗心衰患者的安全性已被广泛证实,但有效性在不同类型的心衰患者有所差别.本文对心衰发生中的NO-sGC-cGMP通路的改变、维利西呱的作用机制及在心衰中的治疗进展进行综述.
Advance in the application of vericiguat in heart failure
The development and progression of heart failure involves vascular endothelial dysfunction,inflammation,and oxidative stress,and this pathophysiological process affects the activity of the nitric oxide(NO)-soluble guanylate cyclase(sGC)-cyclic guano-sine monophosphate(cGMP)signaling pathway.Vericiguat can increase the level of cGMP by stimulating sGC,and as a second mes-senger to activate protein kinases,phosphodiesterases,and subsequent signaling pathways,cGMP can dilate blood vessels,improve coronary blood flow,and inhibit the progression of inflammation and myocardial fibrosis,thereby improving the prognosis of patients with heart failure.At present,several clinical studies have been conducted for vericiguat in the treatment of heart failure with reduced ejection fraction and heart failure with preserved ejection fraction,and its safety in the treatment of heart failure patients has been widely confirmed,but its efficacy varies in different types of heart failure patients.This article reviews the changes in the NO-sGC-cGMP pathway during the onset of heart failure,the mechanism of action of vericiguat,and the advances in vericiguat in the treatment of heart failure.
万方数据
维普
