Exploring PKG signaling as a therapeutic avenue for pressure overload, ischemia, and HFpEF.

IF 4.6 2区 医学 Q1 PHARMACOLOGY & PHARMACY
S Zhazykbayeva, H Budde, M Kaçmaz, Y Zemedie, H Osman, R Hassoun, K Jaquet, I Akin, I El-Battrawy, M Herwig, N Hamdani
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Abstract

Introduction: Heart failure (HF) is a complex and heterogeneous syndrome resulting from any diastolic or systolic dysfunction of the cardiac muscle. In addition to comorbid conditions, pressure overload, and myocardial ischemia are associated with cardiac remodeling which manifests as extracellular matrix (ECM) perturbations, impaired cellular responses, and subsequent ventricular dysfunction.

Areas covered: The current review discusses the main aspects of the cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) pathway (cGMP-PKG) pathway modulators and highlights the promising outcomes of its novel pharmacological boosters.

Expert opinion: Among several signaling pathways involved in the pathogenesis of pressure overload, ischemia and HF with preserved ejection fraction (HFpEF) is cGMP-PKG pathway. This pathway plays a pivotal role in the regulation of cardiac contractility, and modulation of cGMP-PKG signaling, contributing to the development of the diseases. Ventricular cardiomyocytes of HF patients and animal models are known to exhibit reduced cGMP levels and disturbed cGMP signaling including hypophosphorylation of PKG downstream targets. However, restoration of cGMP-PKG signaling improves cardiomyocyte function and promotes cardioprotective effects.

探索 PKG 信号转导作为压力过载、缺血和高房血症的治疗途径。
导言心力衰竭(HF)是由心肌舒张或收缩功能障碍引起的一种复杂的异质性综合征。除合并症外,压力过载和心肌缺血也与心脏重塑有关,重塑表现为细胞外基质(ECM)紊乱、细胞反应受损以及随后的心室功能障碍:本综述讨论了环磷酸鸟苷(cGMP)-蛋白激酶G(PKG)通路(cGMP-PKG)调节剂的主要方面,并重点介绍了新型药理学促进剂的前景:参与压力过载、缺血和射血分数保留型心房颤动(HFpEF)发病机制的几种信号通路之一是cGMP-PKG通路。该通路在调节心脏收缩力和调控 cGMP-PKG 信号转导方面发挥着关键作用,并导致疾病的发生。众所周知,高血压患者和动物模型的心室心肌细胞的 cGMP 水平降低,cGMP 信号转导紊乱,包括 PKG 下游靶点磷酸化不足。然而,恢复 cGMP-PKG 信号传导可改善心肌细胞功能并促进心脏保护作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
8.90
自引率
1.70%
发文量
58
审稿时长
3 months
期刊介绍: The journal evaluates molecules, signalling pathways, receptors and other therapeutic targets and their potential as candidates for drug development. Articles in this journal focus on the molecular level and early preclinical studies. Articles should not include clinical information including specific drugs and clinical trials. The Editors welcome: Reviews covering novel disease targets at the molecular level and information on early preclinical studies and their implications for future drug development. Articles should not include clinical information including specific drugs and clinical trials. Original research papers reporting results of target selection and validation studies and basic mechanism of action studies for investigative and marketed drugs. The audience consists of scientists, managers and decision makers in the pharmaceutical industry, academic researchers working in the field of molecular medicine and others closely involved in R&D.
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