Laboratory of Stem Cells for Tissue Engineering, IRCCS Policlinico San Donato, Milan, Italy.
Department of Arrhythmology, IRCCS Policlinico San Donato, Milan, Italy.
J Cell Physiol. 2021 Jul;236(7):4857-4873. doi: 10.1002/jcp.30235. Epub 2021 Jan 11.
Cardiovascular diseases (CVDs) are the leading cause of death globally and the number of cardiovascular patients, which is estimated to be over 30 million in 2018, represent a challenging issue for the healthcare systems worldwide. Therefore, the identification of novel molecular targets to develop new treatments is an ongoing challenge for the scientific community. In this context, sphingolipids (SLs) have been progressively recognized as potent bioactive compounds that play crucial roles in the modulation of several key biological processes, such as proliferation, differentiation, and apoptosis. Furthermore, SLs involvement in cardiac physiology and pathophysiology attracted much attention, since these molecules could be crucial in the development of CVDs. Among SLs, ceramide and sphingosine-1-phosphate (S1P) represent the most studied bioactive lipid mediators, which are characterized by opposing activities in the regulation of the fate of cardiac cells. In particular, maintaining the balance of the so-called ceramide/S1P rheostat emerged as an important novel therapeutical target to counteract CVDs. Thus, this review aims at critically summarizing the current knowledge about the antithetic roles of ceramide and S1P in cardiomyocytes dysfunctions, highlighting how the modulation of their metabolism through specific molecules, such as myriocin and FTY720, could represent a novel and interesting therapeutic approach to improve the management of CVDs.
心血管疾病 (CVDs) 是全球范围内的主要死因，全球心血管病患者人数估计在 2018 年超过 3000 万，这对全球医疗体系构成了挑战。因此，寻找新的分子靶点以开发新的治疗方法是科学界面临的一个持续挑战。在这种情况下，神经鞘脂类 (SLs) 逐渐被认为是具有生物活性的强效化合物，它们在调节多种关键生物过程（如增殖、分化和凋亡）中起着至关重要的作用。此外，SLs 在心臓生理学和病理生理学中的作用引起了广泛关注，因为这些分子可能在 CVDs 的发展中起关键作用。在 SLs 中，神经酰胺和鞘氨醇-1-磷酸 (S1P) 是研究最多的生物活性脂质介质，它们在调节心脏细胞命运方面具有相反的作用。特别是，维持所谓的神经酰胺/S1P 变阻器的平衡已成为对抗 CVDs 的一个重要新的治疗靶点。因此，本综述旨在批判性地总结关于神经酰胺和 S1P 在心肌细胞功能障碍中的拮抗作用的最新知识，强调通过特定分子（如米诺环素和 FTY720）调节它们的代谢可能是改善 CVDs 管理的一种新的、有趣的治疗方法。
