Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
Department of Pharmacology, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand.
Int J Mol Sci. 2023 Aug 16;24(16):12866. doi: 10.3390/ijms241612866.
Current drugs for treating heart failure (HF), for example, angiotensin II receptor blockers and β-blockers, possess specific target molecules involved in the regulation of the cardiac circulatory system. However, most clinically approved drugs are effective in the treatment of HF with reduced ejection fraction (HFrEF). Novel drug classes, including angiotensin receptor blocker/neprilysin inhibitor (ARNI), sodium-glucose co-transporter-2 (SGLT2) inhibitor, hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker, soluble guanylyl cyclase (sGC) stimulator/activator, and cardiac myosin activator, have recently been introduced for HF intervention based on their proposed novel mechanisms. SGLT2 inhibitors have been shown to be effective not only for HFrEF but also for HF with preserved ejection fraction (HFpEF). In the myocardium, excess cyclic adenosine monophosphate (cAMP) stimulation has detrimental effects on HFrEF, whereas cyclic guanosine monophosphate (cGMP) signaling inhibits cAMP-mediated responses. Thus, molecules participating in cGMP signaling are promising targets of novel drugs for HF. In this review, we summarize molecular pathways of cGMP signaling and clinical trials of emerging drug classes targeting cGMP signaling in the treatment of HF.
目前用于治疗心力衰竭 (HF) 的药物，例如血管紧张素 II 受体阻滞剂和β受体阻滞剂，具有涉及心脏循环系统调节的特定靶分子。然而，大多数临床批准的药物对射血分数降低的心力衰竭 (HFrEF) 的治疗有效。新型药物类别，包括血管紧张素受体阻滞剂/脑啡肽酶抑制剂 (ARNI)、钠-葡萄糖协同转运蛋白 2 (SGLT2) 抑制剂、超极化激活环核苷酸门控 (HCN) 通道阻滞剂、可溶性鸟苷酸环化酶 (sGC) 刺激剂/激活剂和肌球蛋白激活剂，最近已被引入 HF 干预，基于其提出的新机制。SGLT2 抑制剂不仅对 HFrEF 有效，而且对射血分数保留的心力衰竭 (HFpEF) 也有效。在心肌中，过量的环腺苷酸 (cAMP) 刺激对 HFrEF 有不利影响，而环鸟苷酸 (cGMP) 信号抑制 cAMP 介导的反应。因此，参与 cGMP 信号的分子是 HF 新型药物的有前途的靶点。在这篇综述中，我们总结了 cGMP 信号通路以及针对 cGMP 信号通路治疗 HF 的新兴药物类别的临床试验。
