Endocannabinoid Research Group, Institute of Biomolecular Chemistry, National Research Council, Via Campi Flegrei 34, Pozzuoli (NA), Italy.
Department of Science and Technology, University of Sannio, Benevento, Italy.
Clin Sci (Lond). 2019 Apr 4;133(7):853-857. doi: 10.1042/CS20181036. Print 2019 Apr 15.
Emerging evidence attributes to orexins/hypocretins (ORs) a protective function in the regulation of cardiovascular responses, heart rate, and hypertension. However, little is known about any direct effect of orexins in the heart function. This is of special relevance considering that cardiovascular diseases, including myocardial infarction and heart failure, are one of the major causes of mortality in the world. In the article published in (2018) (vol. , 2547-2564), Patel and colleagues investigated the role of orexins in myocardial protection. Intriguingly, they revealed a source of orexin-A (OR-A) and orexin-B (OR-B) in the heart and cardiomyocytes of the rat. More interestingly, these peptides exert a direct effect on the heart rate by acting in an autocrine/paracrine manner on their respective receptors (OXRs). Indeed, OR-B, but not OR-A, by acting through orexin receptor-2 (OX2R), exerts direct cardioprotective effects in heart failure models. OR-B/OX2R signalling enhances myosin light chain (MLC) and troponin-I (TnI) phosphorylation in a dose-dependent manner, leading to an increase in the strength of their twitch contraction. This effect is mediated by extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt phosphorylation, both in the rat myocardial tissue and human heart samples. A negative correlation between OX2R expression and clinical severity of symptoms has been found in patients with heart failure. Thus, in addition to the known central effects of orexins/OX2R, the work of Patel and colleagues ( (2018) , 2547-2564) reports a direct action of OR-B on the heart rate pinpointing to OX2R as a potential therapeutic target for prevention and treatment of cardiovascular disease.
越来越多的证据表明食欲素/下丘脑分泌素 (ORs) 在调节心血管反应、心率和高血压方面具有保护作用。然而，关于食欲素对心脏功能的直接作用知之甚少。考虑到心血管疾病（包括心肌梗死和心力衰竭）是世界上主要的死亡原因之一，这一点尤其重要。在发表于 (2018) (卷。，2547-2564) 的文章中，Patel 和同事们研究了食欲素在心肌保护中的作用。有趣的是，他们在大鼠心脏和心肌细胞中发现了食欲素-A (OR-A) 和食欲素-B (OR-B) 的来源。更有趣的是，这些肽通过在其各自的受体 (OXR) 上以自分泌/旁分泌的方式发挥直接作用来影响心率。事实上，OR-B 通过作用于食欲素受体-2 (OX2R) 发挥直接的心脏保护作用，而 OR-A 则没有。OR-B/OX2R 信号以剂量依赖的方式增强肌球蛋白轻链 (MLC) 和肌钙蛋白 I (TnI) 的磷酸化，导致其抽搐收缩强度增加。这种作用是由细胞外信号调节激酶 1/2 (ERK1/2) 和 Akt 磷酸化介导的，在大鼠心肌组织和人心脏样本中均如此。在心力衰竭患者中发现 OX2R 表达与临床症状严重程度呈负相关。因此，除了已知的食欲素/OX2R 的中枢作用外，Patel 和同事的工作 ( (2018) ，2547-2564) 还报告了 OR-B 对心率的直接作用，指出 OX2R 可能是预防和治疗心血管疾病的潜在治疗靶点。
