Cardiology; ASST Spedali Civili di Brescia and Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, P.zza Spedali Civili 1, 25123, Brescia, Italy.
Institute of Life Sciences, Scuola Superiore Sant'Anna, Piazza Martiri della Libertà 33, 56124, Pisa, Italy.
Curr Cardiol Rep. 2021 Aug 19;23(10):144. doi: 10.1007/s11886-021-01580-6.
The nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway plays an important role in the regulation of cardiovascular function, and it is disrupted in heart failure (HF), resulting in decreased protection against myocardial injury. Impaired NO-sGC-cGMP signaling in HF is secondary to reduced NO bioavailability and altered redox state of sGC, which becomes less responsive to NO. The sGC activator cinaciguat increases cGMP levels by direct NO-independent activation of sGC and may be particularly effective in conditions of increased oxidative stress and endothelial dysfunction, and therefore reduced NO levels, at the expense of a greater risk of hypotension. Conversely, sGC stimulators (riociguat and vericiguat) enhance sGC sensitivity to endogenous NO, thus exerting a more physiological action.
Clinical trials have suggested the benefit of vericiguat in patients with high-risk HF; in particular, a lower incidence of death from cardiovascular causes or HF hospitalization. Adding vericiguat may be considered in individual patients with HF, and reduced left ventricular ejection fraction (HFrEF) particularly those at higher risk of HF hospitalization.
一氧化氮（NO）-可溶性鸟苷酸环化酶（sGC）-环鸟苷酸（cGMP）途径在心血管功能调节中起着重要作用，在心力衰竭（HF）中被破坏，导致心肌损伤的保护作用降低。HF 中 NO-sGC-cGMP 信号转导受损是由于 NO 生物利用度降低和 sGC 氧化还原状态改变，导致 sGC 对 NO 的反应性降低。sGC 激活剂西那卡塞通过直接非依赖性激活 sGC 增加 cGMP 水平，在氧化应激和内皮功能障碍增加、NO 水平降低的情况下可能特别有效，因此低血压的风险增加。相反，sGC 刺激剂（利奥西呱和维立西呱）增强 sGC 对内源性 NO 的敏感性，从而发挥更生理的作用。
临床试验表明维立西呱可使高危 HF 患者获益；特别是心血管原因或 HF 住院导致的死亡率降低。HF 患者，特别是射血分数降低的心力衰竭（HFrEF）患者，尤其是 HF 住院风险较高的患者，可考虑加用维立西呱。
