Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University Malaysia Sabah, Kota Kinabalu 88400, Sabah, Malaysia.
Health through Exercise and Active Living (HEAL) Research Unit, Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, Kota Kinabalu 88400, Sabah, Malaysia.
Molecules. 2023 Feb 23;28(5):2102. doi: 10.3390/molecules28052102.
Myocardial remodelling is a molecular, cellular, and interstitial adaptation of the heart in response to altered environmental demands. The heart undergoes reversible physiological remodelling in response to changes in mechanical loading or irreversible pathological remodelling induced by neurohumoral factors and chronic stress, leading to heart failure. Adenosine triphosphate (ATP) is one of the potent mediators in cardiovascular signalling that act on the ligand-gated (P2X) and G-protein-coupled (P2Y) purinoceptors via the autocrine or paracrine manners. These activations mediate numerous intracellular communications by modulating the production of other messengers, including calcium, growth factors, cytokines, and nitric oxide. ATP is known to play a pleiotropic role in cardiovascular pathophysiology, making it a reliable biomarker for cardiac protection. This review outlines the sources of ATP released under physiological and pathological stress and its cell-specific mechanism of action. We further highlight a series of cardiovascular cell-to-cell communications of extracellular ATP signalling cascades in cardiac remodelling, which can be seen in hypertension, ischemia/reperfusion injury, fibrosis, hypertrophy, and atrophy. Finally, we summarize current pharmacological intervention using the ATP network as a target for cardiac protection. A better understanding of ATP communication in myocardial remodelling could be worthwhile for future drug development and repurposing and the management of cardiovascular diseases.
心肌重构是心脏对环境需求改变的一种分子、细胞和间质适应。心脏对机械负荷的变化或神经激素因素和慢性应激引起的不可逆病理性重构做出可逆的生理重构，导致心力衰竭。三磷酸腺苷（ATP）是心血管信号转导中的一种有效介质，通过自分泌或旁分泌方式作用于配体门控（P2X）和 G 蛋白偶联（P2Y）嘌呤能受体。这些激活通过调节其他信使（包括钙、生长因子、细胞因子和一氧化氮）的产生来介导许多细胞内通讯。已知 ATP 在心血管病理生理学中发挥多种作用，使其成为心脏保护的可靠生物标志物。本综述概述了在生理和病理应激下释放的 ATP 的来源及其在细胞特异性中的作用机制。我们进一步强调了细胞外 ATP 信号级联在心脏重构中的一系列心血管细胞间通讯，这些通讯可见于高血压、缺血/再灌注损伤、纤维化、肥大和萎缩。最后，我们总结了目前使用 ATP 网络作为心脏保护靶点的药理学干预。更好地理解心肌重构中的 ATP 通讯可能有助于未来的药物开发和再利用以及心血管疾病的管理。
