Department of Cellular and Translational Physiology, Institute of Physiology, Ruhr University Bochum, Bochum, Germany.
Institut für Forschung und Lehre (IFL), Molecular and Experimental Cardiology, Ruhr University Bochum, Bochum, Germany.
Expert Opin Ther Targets. 2024 Oct;28(10):857-873. doi: 10.1080/14728222.2024.2400093. Epub 2024 Sep 27.
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.
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.
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.
心力衰竭（HF）是一种复杂且异质性的综合征，源于心肌的舒张或收缩功能障碍。除了合并症外，压力超负荷和心肌缺血与心脏重构有关，其表现为细胞外基质（ECM）的改变、细胞应答受损以及随后的心室功能障碍。
本综述讨论了环鸟苷酸单磷酸（cGMP）-蛋白激酶 G（PKG）途径（cGMP-PKG）途径调节剂的主要方面，并强调了其新型药理学激动剂的有前途的结果。
在与压力超负荷、缺血和射血分数保留的心力衰竭（HFpEF）相关的几种参与发病机制的信号通路中，cGMP-PKG 通路是其中之一。该途径在调节心肌收缩性和调节 cGMP-PKG 信号中起着关键作用，有助于疾病的发展。HF 患者和动物模型的心室心肌细胞已知表现出 cGMP 水平降低和 cGMP 信号紊乱，包括 PKG 下游靶标的低磷酸化。然而，恢复 cGMP-PKG 信号可改善心肌细胞功能并促进心脏保护作用。
