Xu Chuanhui, Rodríguez-Carrio Javier, Xie Yang, Hu Fanlei, Chong Wei Ming, Hou Han Wei, Dalan Rinkoo, Leong Khai Pang
Department of Rheumatology, Allergy and Immunology, Tan Tock Seng Hospital, 11 Jln Tan Tock Seng, Singapore 308433, Singapore.
Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore.
Int J Mol Sci. 2025 Sep 2;26(17):8514. doi: 10.3390/ijms26178514.
Patients with rheumatoid arthritis (RA) have an increased risk of cardiovascular disease (CVD) that cannot be fully explained by traditional cardiometabolic risk factors. The observed 'lipid paradox', where RA patients with lower total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels exhibit higher CVD risk, may be attributed to post-translational modifications (PTMs). These lipoprotein PTMs likely arise from inflammatory pathways. While PTMs like citrullination and carbamylation are well recognized in RA joint pathology, their occurrence in other protein compartments and their role in CVD have been less well explored. This scoping review summarizes the current literature on PTMs of lipoproteins, including oxidation, nitration, carbamylation, and citrullination, and their impacts on CVD in RA. We also discuss immune responses to these PTMs, their interactions with scavenger receptors, and the effects of disease-modifying antirheumatic drugs. Further research on PTMs may uncover new pathways linking autoimmunity, inflammation, and vascular damage, offering novel diagnostic and therapeutic opportunities for RA-associated CVD.
类风湿性关节炎（RA）患者患心血管疾病（CVD）的风险增加，而传统的心脏代谢风险因素无法完全解释这一现象。所观察到的“脂质悖论”，即总胆固醇和低密度脂蛋白胆固醇（LDL-C）水平较低的RA患者表现出较高的CVD风险，可能归因于翻译后修饰（PTM）。这些脂蛋白PTM可能源于炎症途径。虽然瓜氨酸化和氨甲酰化等PTM在RA关节病理中已得到充分认识，但它们在其他蛋白质区室中的发生情况及其在CVD中的作用尚未得到充分研究。本综述总结了目前关于脂蛋白PTM的文献，包括氧化、硝化、氨甲酰化和瓜氨酸化，以及它们对RA患者CVD的影响。我们还讨论了对这些PTM的免疫反应、它们与清道夫受体的相互作用以及改善病情抗风湿药物的作用。对PTM的进一步研究可能会揭示连接自身免疫、炎症和血管损伤的新途径，为RA相关CVD提供新的诊断和治疗机会。
