Nikolic Maja, Srejovic Ivan, Jovic Jovana Joksimovic, Sretenovic Jasmina, Jeremic Jovana, Cekerevac Ivan, Simovic Stefan, Djokovic Danijela, Muric Nemanja, Stojic Vladislava, Bolevich Stefani, Bolevich Sergey, Jakovljevic Vladimir
Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia.
Department of Pharmacology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia.
Rev Cardiovasc Med. 2022 Jun 24;23(7):238. doi: 10.31083/j.rcm2307238. eCollection 2022 Jul.
As the ultimate pathophysiological event, heart failure (HF) may arise from various cardiovascular (CV) conditions, including sustained pressure/volume overload of the left ventricle, myocardial infarction or ischemia, and cardiomyopathies. Sacubitril/valsartan (S/V; formerly termed as LCZ696), a first-in-class angiotensin receptor/neprilysin inhibitor, brought a significant shift in the management of HF with reduced ejection fraction by modulating both renin-angiotensin-aldosterone system (angiotensin II type I receptor blockage by valsartan) and natriuretic peptide system (neprilysin inhibition by sacubitril) pathways. Besides, the efficacy of S/V has been also investigated in the setting of other CV pathologies which are during their pathophysiological course and progression deeply interrelated with HF. However, its mechanism of action is not entirely clarified, suggesting other off-target benefits contributing to its cardioprotection. In this review article our goal was to highlight up-to-date clinical and experimental evidence on S/V cardioprotective effects, as well as most discussed molecular mechanisms achieved by this dual-acting compound. Although S/V was extensively investigated in HF patients, additional large studies are needed to elucidate its effects in the setting of other CV conditions. Furthermore, with its antiinflamatory potential, this agent should be investigated in animal models of inflammatory heart diseases, such as myocarditis, while it may possibly improve cardiac dysfunction as well as inflammatory response in this pathophysiological setting. Also, discovering other signalling pathways affected by S/V should be of particular interest for basic researches, while it can provide additional understanding of its cardioprotective mechanisms.
作为最终的病理生理事件，心力衰竭（HF）可能由多种心血管（CV）疾病引起，包括左心室持续压力/容量超负荷、心肌梗死或缺血以及心肌病。沙库巴曲/缬沙坦（S/V；原称LCZ696），一种一流的血管紧张素受体/中性肽链内切酶抑制剂，通过调节肾素-血管紧张素-醛固酮系统（缬沙坦阻断血管紧张素II 1型受体）和利钠肽系统（沙库巴曲抑制中性肽链内切酶）途径，在射血分数降低的心力衰竭管理方面带来了重大转变。此外，S/V在其他CV疾病中的疗效也已在其病理生理过程和进展与HF密切相关的背景下进行了研究。然而，其作用机制尚未完全阐明，提示可能存在其他脱靶益处有助于其心脏保护作用。在这篇综述文章中，我们的目标是强调关于S/V心脏保护作用的最新临床和实验证据，以及这种双重作用化合物所实现的最受讨论的分子机制。尽管S/V已在HF患者中进行了广泛研究，但仍需要更多大型研究来阐明其在其他CV疾病背景下的作用。此外，鉴于其抗炎潜力，该药物应在炎症性心脏病（如心肌炎）的动物模型中进行研究，因为它可能在这种病理生理背景下改善心脏功能障碍以及炎症反应。此外，发现受S/V影响的其他信号通路应是基础研究特别感兴趣的，因为这可以提供对其心脏保护机制的更多理解。
