Matsiras Dionysis, Ventoulis Ioannis, Verras Christos, Bistola Vasiliki, Bezati Sofia, Fyntanidou Barbara, Polyzogopoulou Effie, Parissis John T
Department of Emergency Medicine, Attikon University Hospital, National and Kapodistrian University of Athens, Rimini 1, 12462 Athens, Greece.
Department of Occupational Therapy, University of Western Macedonia, Keptse Area, 50200 Ptolemaida, Greece.
J Clin Med. 2025 Apr 13;14(8):2657. doi: 10.3390/jcm14082657.
Heart failure (HF) is a challenging clinical syndrome with high morbidity and mortality rates. Along the spectrum of cardiovascular diseases, HF constitutes an ever-expanding area of research aiming at combating the associated mortality and improving the prognosis of patients with HF. Although natriuretic peptides have an established role among biomarkers in HF diagnosis and prognosis, several novel biomarkers reflecting the complex pathophysiology of HF are under investigation for their ability to predict adverse clinical outcomes in HF. Proenkephalin 119-159 (PENK) is a non-functional peptide belonging to the enkephalin family of the endogenous opioid system and is considered a surrogate biomarker of the biologically active enkephalin peptides. PENK has demonstrated promising results in predicting short- and long-term mortality, readmission rates, and worsening renal function in patients with HF. Indeed, in the setting of HF, the levels of both active enkephalins and their surrogate PENK are elevated and are associated with a dismal prognosis. However, the biological effects of PENK remain largely unknown. Thus, it is crucial to gain a deeper insight into both the physiology of the enkephalin peptide family and the enkephalin-mediated cardiovascular regulation. In order to elucidate the complex pathophysiological mechanisms that lead to the upregulation of enkephalins in patients with HF, as well as the potential clinical implications of elevated enkephalins and PENK levels in this patient population, the present review will describe the physiology and distribution of the endogenous opioid peptides and their corresponding opioid receptors, with a particular focus on the action of enkephalins. The effects of the enkephalin peptides will be analyzed in both healthy subjects and patients with HF, especially with regard to their role in the regulation of cardiovascular and renal function. The review will also discuss the findings of recent studies that have explored the prognostic value of PENK in patients with HF.
心力衰竭（HF）是一种具有挑战性的临床综合征，发病率和死亡率都很高。在心血管疾病的范畴内，HF构成了一个不断扩大的研究领域，旨在对抗相关死亡率并改善HF患者的预后。尽管利钠肽在HF诊断和预后的生物标志物中已确立了作用，但几种反映HF复杂病理生理学的新型生物标志物因其预测HF不良临床结局的能力正在接受研究。前脑啡肽原119 - 159（PENK）是一种无功能的肽，属于内源性阿片系统的脑啡肽家族，被认为是生物活性脑啡肽肽的替代生物标志物。PENK在预测HF患者的短期和长期死亡率、再入院率以及肾功能恶化方面已显示出有前景的结果。事实上，在HF的情况下，活性脑啡肽及其替代物PENK的水平都会升高，且与不良预后相关。然而，PENK的生物学效应在很大程度上仍不清楚。因此，深入了解脑啡肽肽家族的生理学以及脑啡肽介导的心血管调节至关重要。为了阐明导致HF患者脑啡肽上调的复杂病理生理机制，以及该患者群体中脑啡肽和PENK水平升高的潜在临床意义，本综述将描述内源性阿片肽及其相应阿片受体的生理学和分布，特别关注脑啡肽的作用。将分析脑啡肽肽在健康受试者和HF患者中的作用，尤其是它们在心血管和肾功能调节中的作用。本综述还将讨论最近探索PENK在HF患者中预后价值的研究结果。
