Bhat Owais Mohmad, Mir Rakeeb Ahmad, Nehvi Iqra Bashir, Wani Nissar Ahmad, Dar Abid Hamid, Zargar M Afzal
Department of Biotechnology, School of Life Sciences, Central University of Kashmir, Ganderbal, India.
Department of Clinical Biochemistry, SKIMS, Soura, Srinagar, India.
Int J Cardiol Heart Vasc. 2024 Jul 23;53:101469. doi: 10.1016/j.ijcha.2024.101469. eCollection 2024 Aug.
Sphingolipids are eighteen carbon alcohol lipids synthesized from non-sphingolipid precursors in the endoplasmic reticulum (ER). The sphingolipids serve as precursors for a vast range of moieties found in our cells that play a critical role in various cellular processes, including cell division, senescence, migration, differentiation, apoptosis, pyroptosis, autophagy, nutrition intake, metabolism, and protein synthesis. In CVDs, different subclasses of sphingolipids and other derived molecules such as sphingomyelin (SM), ceramides (CERs), and sphingosine-1-phosphate (S1P) are directly related to diabetic cardiomyopathy, dilated cardiomyopathy, myocarditis, ischemic heart disease (IHD), hypertension, and atherogenesis. Several genome-wide association studies showed an association between genetic variations in sphingolipid pathway genes and the risk of CVDs. The sphingolipid pathway plays an important role in the biogenesis and secretion of exosomes. Small extracellular vesicles (sEVs)/ exosomes have recently been found as possible indicators for the onset of CVDs, linking various cellular signaling pathways that contribute to the disease progression. Important features of EVs like biocompatibility, and crossing of biological barriers can improve the pharmacokinetics of drugs and will be exploited to develop next-generation drug delivery systems. In this review, we have comprehensively discussed the role of sphingolipids, and sphingolipid metabolites in the development of CVDs. In addition, concise deliberations were laid to discuss the role of sEVs/exosomes in regulating the pathophysiological processes of CVDs and the exosomes as therapeutic targets.
鞘脂是在内质网（ER）中由非鞘脂前体合成的含有18个碳原子的醇类脂质。鞘脂是我们细胞中多种成分的前体，在各种细胞过程中发挥关键作用，包括细胞分裂、衰老、迁移、分化、凋亡、焦亡、自噬、营养摄取、代谢和蛋白质合成。在心血管疾病（CVDs）中，不同亚类的鞘脂和其他衍生分子，如鞘磷脂（SM）、神经酰胺（CERs）和1-磷酸鞘氨醇（S1P），与糖尿病性心肌病、扩张型心肌病、心肌炎、缺血性心脏病（IHD）、高血压和动脉粥样硬化的发生直接相关。几项全基因组关联研究表明，鞘脂途径基因的遗传变异与心血管疾病风险之间存在关联。鞘脂途径在细胞外囊泡的生物发生和分泌中起重要作用。最近发现，小细胞外囊泡（sEVs）/细胞外囊泡可能是心血管疾病发病的指标，它连接了导致疾病进展的各种细胞信号通路。细胞外囊泡的重要特性，如生物相容性和跨越生物屏障的能力，可以改善药物的药代动力学，并将被用于开发下一代药物递送系统。在这篇综述中，我们全面讨论了鞘脂及其代谢产物在心血管疾病发展中的作用。此外，还简要讨论了sEVs/细胞外囊泡在调节心血管疾病病理生理过程中的作用以及将细胞外囊泡作为治疗靶点的情况。
