Zhao Meng, Bian Rutao, Xu Xuegong, Zhang Junpeng, Zhang Li, Zheng Yi
The First Clinical Medical College of Henan University of Chinese Medicine, Zhengzhou, Henan Province, People's Republic of China.
Department of Cardiology, Zhengzhou Hospital of Traditional Chinese Medicine, Zhengzhou, Henan Province, People's Republic of China.
J Inflamm Res. 2025 Apr 23;18:5477-5498. doi: 10.2147/JIR.S515757. eCollection 2025.
Sphingolipids are essential components of cell membranes and lipoproteins. They are synthesized de novo in the endoplasmic reticulum and subsequently undergo various enzymatic modifications in different organelles, giving rise to a diverse range of biologically active compounds. These molecules play a critical role in regulating cell growth, senescence, migration, apoptosis, and signaling. In recent years, the sphingolipid metabolic pathway has been recognized as a key factor in heart failure (HF) pathophysiology. Abnormal levels of sphingolipid metabolites, such as ceramide (Cer) and sphingomyelin (SM), contribute to oxidative stress and inflammatory responses, ultimately promoting cardiomyocyte apoptosis. Conversely, sphingosine-1-phosphate (S1P) and ceramide-1-phosphate (C1P) regulate vascular function and influence cardiac remodeling. Additionally, enzymes such as diacylglycerol acyltransferase 1 (DGAT1) and sphingosine-1-phosphate lyase 1 (SGPL1) modulate cardiac lipid metabolism. Given their role in HF progression, monitoring sphingolipid alterations offers potential as valuable biomarkers for assessing disease severity, prognosis, and diagnosis. Given the complexity of sphingolipid metabolism and its involvement in diverse regulatory biological processes, a comprehensive understanding of its roles at both the cellular and organismal levels in physiopathology remains incomplete. Therefore, this review aims to explore the physiological functions, regulatory mechanisms, and therapeutic potential of sphingolipid metabolism. It will summarize the specific molecular mechanisms driving key pathological processes in HF, including ventricular remodeling, myocardial fibrosis, vascular dysfunction, and metabolic disorders. Finally, the review will highlight targeted sphingolipid metabolites as potential therapeutic strategies, offering new insights into HF diagnosis and treatment, with the goal of advancing adjunctive clinical therapies.
鞘脂是细胞膜和脂蛋白的重要组成部分。它们在内质网中从头合成，随后在不同细胞器中经历各种酶促修饰，产生多种生物活性化合物。这些分子在调节细胞生长、衰老、迁移、凋亡和信号传导中起关键作用。近年来，鞘脂代谢途径已被认为是心力衰竭（HF）病理生理学中的一个关键因素。鞘脂代谢物水平异常，如神经酰胺（Cer）和鞘磷脂（SM），会导致氧化应激和炎症反应，最终促进心肌细胞凋亡。相反，1-磷酸鞘氨醇（S1P）和1-磷酸神经酰胺（C1P）调节血管功能并影响心脏重塑。此外，二酰甘油酰基转移酶1（DGAT1）和1-磷酸鞘氨醇裂解酶1（SGPL1）等酶调节心脏脂质代谢。鉴于它们在HF进展中的作用，监测鞘脂变化有可能成为评估疾病严重程度、预后和诊断的有价值生物标志物。鉴于鞘脂代谢的复杂性及其参与多种调节性生物过程，在生理病理学中对其在细胞和机体水平上的作用的全面理解仍然不完整。因此，本综述旨在探讨鞘脂代谢的生理功能、调节机制和治疗潜力。它将总结驱动HF关键病理过程的具体分子机制，包括心室重塑、心肌纤维化、血管功能障碍和代谢紊乱。最后，本综述将强调靶向鞘脂代谢物作为潜在的治疗策略，为HF诊断和治疗提供新的见解，以期推进辅助临床治疗。
