Department of Life Science, Gachon University, Sungnam, Gyeonggido, South Korea.
Adv Exp Med Biol. 2022;1372:31-46. doi: 10.1007/978-981-19-0394-6_3.
Atherosclerosis is the formation of fibrofatty lesions in the arterial wall, and this inflammatory state of the artery is the main cause of advanced pathological processes, including myocardial infarction and stroke. Dyslipidemic conditions with excess cholesterol accumulate within the arterial vessel wall and initiate atherogenic processes. Following vascular reaction and lipid accumulation, the vascular wall gradually thickens. Together with the occurrence of local inflammation, early atherosclerotic lesions lead to advanced pathophysiological events, plaque rupture, and thrombosis. Ceramide and sphingomyelin have emerged as major risk factors for atherosclerosis and coronary artery disease. Currently, the clinical association between de novo sphingolipid biosynthesis and coronary artery disease has been established. Furthermore, therapeutic strategies to modulate this pathway, especially those involving serine palmitoyltransferase and sphingomyelin synthase, against atherosclerosis, cancer, type 2 diabetes, and non-alcoholic fatty liver disease are actively under development. In this chapter, we focus on the relationship between de novo sphingolipid biosynthesis and coronary artery disease.
动脉粥样硬化是动脉壁中纤维脂肪病变的形成，而动脉的这种炎症状态是导致包括心肌梗死和中风在内的高级病理过程的主要原因。胆固醇过多的血脂异常状况在动脉血管壁内积聚，并引发动脉粥样硬化过程。在血管反应和脂质积累之后，血管壁逐渐变厚。随着局部炎症的发生，早期动脉粥样硬化病变导致高级病理生理事件、斑块破裂和血栓形成。神经酰胺和鞘磷脂已成为动脉粥样硬化和冠心病的主要危险因素。目前，已经确定了从头合成鞘脂与冠心病之间的临床关联。此外，针对动脉粥样硬化、癌症、2 型糖尿病和非酒精性脂肪肝疾病调节该途径的治疗策略，特别是涉及丝氨酸棕榈酰转移酶和鞘磷脂合酶的策略，正在积极开发中。在本章中，我们重点介绍从头合成鞘脂与冠心病之间的关系。
