Cardiometabolic diseases (CMDs) are major contributors to global mortality, emphasizing the critical need for novel therapeutic interventions. Hydrogen sulfide (H₂S) has garnered enormous attention as a significant gasotransmitter with various physiological, pathophysiological, and pharmacological impacts within mammalian cardiometabolic systems. In addition to its roles in attenuating oxidative stress and inflammatory response, burgeoning research emphasizes the significance of H₂S in regulating proteins via persulfidation, a well known modification intricately associated with the pathogenesis of CMDs. This review seeks to investigate recent updates on the physiological actions of endogenous H₂S and the pharmacological roles of various H₂S donors in addressing diverse aspects of CMDs across cellular, animal, and clinical studies. Of note, advanced methodologies, including multiomics, intestinal microflora analysis, organoid, and single-cell sequencing techniques, are gaining traction due to their ability to offer comprehensive insights into biomedical research. These emerging approaches hold promise in characterizing the pharmacological roles of H₂S in health and diseases. We will critically assess the current literature to clarify the roles of H₂S in diseases while also delineating the opportunities and challenges they present in H₂S-based pharmacotherapy for CMDs.

中文翻译：

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硫化氢及其供体在心脏代谢疾病中的药理学


心脏代谢疾病（CMD）是全球死亡率的主要原因，这凸显了对新型治疗干预措施的迫切需要。硫化氢 (H ₂ S) 作为一种重要的气体递质，在哺乳动物心脏代谢系统中具有多种生理、病理生理和药理学影响，引起了极大的关注。除了其在减轻氧化应激和炎症反应方面的作用之外，新兴的研究还强调了 H ₂ S 通过过硫化作用调节蛋白质的重要​​性，这是一种与 CMD 发病机制密切相关的众所周知的修饰。本综述旨在探讨内源性 H ₂ S 生理作用的最新进展，以及各种 H ₂ S 供体在细胞、动物和临床研究中解决 CMD 不同方面的药理学作用。值得注意的是，先进的方法，包括多组学、肠道微生物群分析、类器官和单细胞测序技术，由于能够为生物医学研究提供全面的见解而受到关注。这些新兴方法有望表征 H ₂ S 在健康和疾病中的药理作用。我们将严格评估当前文献，以阐明 H ₂ S 在疾病中的作用，同时描述它们在基于 H ₂ S 的 CMD 药物治疗中带来的机遇和挑战。