PDF(Pubmed)
Abstract：
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.
摘要：
鞘脂是由内质网(ER)中的非鞘脂前体合成的十八碳醇脂质。鞘脂作为我们细胞中发现的大量部分的前体，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,营养摄入，新陈代谢，和蛋白质合成。在CVD中,不同亚类的鞘脂和其他衍生分子，如鞘磷脂（SM），神经酰胺（CER），鞘氨醇-1-磷酸（S1P）与糖尿病心肌病直接相关，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。几项全基因组关联研究表明，鞘脂途径基因的遗传变异与CVD风险之间存在关联。鞘脂途径在外泌体的生物发生和分泌中起重要作用。最近发现小的细胞外囊泡（sEV）/外泌体是CVD发作的可能指标，连接有助于疾病进展的各种细胞信号传导途径。电动汽车的重要特征，如生物相容性，和跨越生物屏障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。在这次审查中,我们已经全面讨论了鞘脂的作用，和鞘脂代谢产物在CVD的发展中。此外,进行了简洁的讨论,讨论了sEV/外泌体在调节CVD的病理生理过程中的作用,并将外泌体作为治疗靶标.
