Department of Geriatric Cardiology, National Clinical Research Center of Geriatrics Disease, Beijing Key Laboratory of Precision Medicine for Chronic Heart Failure, Chinese People's Liberation Army General Hospital, Beijing, China.
Department of Cardiology, Hainan Hospital of Chinese People's Liberation Army General Hospital, Beijing, China.
Curr Top Med Chem. 2019;19(20):1850-1866. doi: 10.2174/1568026619666190826163536.
Notwithstanding substantial improvements in diagnosis and treatment, Heart Failure (HF) remains a major disease burden with high prevalence and poor outcomes worldwide. Natriuretic Peptides (NPs) modulate whole cardiovascular system and exhibit multiple cardio-protective effects, including the counteraction of the Renin-Angiotensin-Aldosterone System (RAAS) and Sympathetic Nervous System (SNS), promotion of vasodilatation and natriuresis, and inhibition of hypertrophy and fibrosis. Novel pharmacological therapies based on NPs may achieve a valuable shift in managing patients with HF from inhibiting RAAS and SNS to a reversal of neurohormonal imbalance. Enhancing NP bioavailability through exogenous NP administration and inhibiting Neutral Endopeptidase (NEP) denotes valuable therapeutic strategies for HF. On the one hand, NEP-resistant NPs may be more specific as therapeutic choices in patients with HF. On the other hand, NEP Inhibitors (NEPIs) combined with RAAS inhibitors have proved to exert beneficial effects and reduce adverse events in patients with HF. Highly effective and potentially safe Angiotensin Receptor Blocker Neprilysin Inhibitors (ARNIs) have been developed after the failure of NEPIs and Vasopeptidase Inhibitors (VPIs) due to lacking efficacy and safety. Therapeutic progress and knowledge basis on the NP system in HF are summarized in the current review.
尽管在诊断和治疗方面取得了重大进展，但心力衰竭（HF）仍然是一种全球范围内负担较重的主要疾病，其患病率高，预后差。利钠肽（NPs）调节整个心血管系统，具有多种心脏保护作用，包括拮抗肾素-血管紧张素-醛固酮系统（RAAS）和交感神经系统（SNS），促进血管舒张和利钠作用，并抑制肥大和纤维化。基于 NPs 的新型药理学治疗方法可能会实现对 HF 患者管理的重要转变，从抑制 RAAS 和 SNS 转变为逆转神经激素失衡。通过外源性 NPs 给药来提高 NPs 的生物利用度和抑制中性内肽酶（NEP）是治疗 HF 的有价值的治疗策略。一方面，NEP 抗性 NPs 可能更适合作为 HF 患者的治疗选择。另一方面，NEP 抑制剂（NEPIs）与 RAAS 抑制剂联合使用已被证明可在 HF 患者中发挥有益作用并减少不良事件。由于缺乏疗效和安全性，NEPIs 和血管肽酶抑制剂（VPIs）失败后，开发出了高效且潜在安全的血管紧张素受体脑啡肽酶抑制剂（ARNIs）。本综述总结了 HF 中 NP 系统的治疗进展和知识基础。
