Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, 10043, Orbassano, TO), Italy.
National Institute for Cardiovascular Research (INRC), 40126, Bologna, Italy.
Basic Res Cardiol. 2024 Aug;119(4):509-544. doi: 10.1007/s00395-024-01061-1. Epub 2024 Jun 15.
Despite recent progress, ischemic heart disease poses a persistent global challenge, driving significant morbidity and mortality. The pursuit of therapeutic solutions has led to the emergence of strategies such as ischemic preconditioning, postconditioning, and remote conditioning to shield the heart from myocardial ischemia/reperfusion injury (MIRI). These ischemic conditioning approaches, applied before, after, or at a distance from the affected organ, inspire future therapeutic strategies, including pharmacological conditioning. Gasotransmitters, comprising nitric oxide, hydrogen sulfide, sulfur dioxide, and carbon monoxide, play pivotal roles in physiological and pathological processes, exhibiting shared features such as smooth muscle relaxation, antiapoptotic effects, and anti-inflammatory properties. Despite potential risks at high concentrations, physiological levels of gasotransmitters induce vasorelaxation and promote cardioprotective effects. Noble gases, notably argon, helium, and xenon, exhibit organ-protective properties by reducing cell death, minimizing infarct size, and enhancing functional recovery in post-ischemic organs. The protective role of noble gases appears to hinge on their modulation of molecular pathways governing cell survival, leading to both pro- and antiapoptotic effects. Among noble gases, helium and xenon emerge as particularly promising in the field of cardioprotection. This overview synthesizes our current understanding of the roles played by gasotransmitters and noble gases in the context of MIRI and cardioprotection. In addition, we underscore potential future developments involving the utilization of noble gases and gasotransmitter donor molecules in advancing cardioprotective strategies.
尽管最近取得了进展，但缺血性心脏病仍然是一个全球性的持续挑战，导致了大量的发病率和死亡率。为了寻找治疗方法，人们提出了缺血预处理、后处理和远程预处理等策略，以保护心脏免受心肌缺血/再灌注损伤（MIRI）。这些缺血预处理策略应用于受影响器官之前、之后或在远处，可以启发未来的治疗策略，包括药物预处理。气体信号分子包括一氧化氮、硫化氢、二氧化硫和一氧化碳，在生理和病理过程中发挥着关键作用，它们具有平滑肌松弛、抗细胞凋亡和抗炎等共同特征。尽管在高浓度下存在潜在风险，但生理水平的气体信号分子可诱导血管舒张并促进心脏保护作用。稀有气体，特别是氩气、氦气和氙气，通过减少细胞死亡、最小化梗塞面积和增强缺血后器官的功能恢复，发挥器官保护作用。稀有气体的保护作用似乎取决于它们对调节细胞存活的分子途径的调制，从而产生促凋亡和抗凋亡作用。在稀有气体中，氦气和氙气在心脏保护领域显示出特别有希望的应用前景。这篇综述综合了我们目前对气体信号分子和稀有气体在 MIRI 和心脏保护中的作用的理解。此外，我们强调了在推进心脏保护策略中利用稀有气体和气体信号分子供体分子的潜在未来发展。
