RNA甲基化、代谢重编程与肺动脉高压  

RNA methylation,metabolic reprogramming and pulmonary hypertension

作　　者：胡丽[1] 沈乐瑶 甘雄康 张雨辉 奉雨心 王杰[1] 陈峰[1,2] Li Hu;Yueyao Shen;Xiongkang Gan;Yuhui Zhang;Yuxin Feng;Jie Wang;Feng Chen(Department of Forensic Medicine,School of Basic Medical Sciences,Nanjing Medical University,Nanjing 211166,China;Key Laboratory of Targeted Intervention of Cardiovascular Disease,Collaborative Innovation Center for Cardiovascular Disease Translational Medicine,Nanjing Medical University,Nanjing 211166,China)

机构地区：[1]南京医科大学基础医学院法医学系,南京211166 [2]南京医科大学心血管病转化医学协同创新中心,南京211166

出　　处：《科学通报》2024年第13期1698-1714,共17页Chinese Science Bulletin

基　　金：国家自然科学基金(82200057,82300069,82225023,82121001);江苏省基础研究计划自然科学基金(BK20220321,18KJB340002,BK20230304)资助。

摘　　要：脉高压(pulmonary hypertension,PH)是一种以肺血管重构为主要病理特征的临床综合征,患者肺血管阻力和肺动脉压力升高,最终因右心衰竭而死亡.近年来,PH血管重构的分子机制研究逐步深入,RNA甲基化作为当前生命科学领域的研究热点,被证实在PH进程中发挥着多种调节作用,包括参与肺血管平滑肌细胞表型转化、内皮细胞间质转化和巨噬细胞免疫炎症等过程.同时,大量的研究表明,PH进程中多种肺血管细胞均存在着异常的代谢重编程,进而加剧血管重构的发生.多项研究显示,RNA甲基化修饰和代谢重编程可以相互调控参与疾病的发生,但两者是否可以相互调控协同促进PH的发生发展目前尚不明确.基于此,本文系统梳理了RNA甲基化、代谢重编程及其与PH发病机制的最新研究进展,并展望了三者之间潜在的生物学联系,期望能够为PH血管重构的发病机制研究及其靶向干预提供新思路.Pulmonary hypertension(PH)is a progressive disease characterized by pulmonary vascular remodeling,sustained elevated pulmonary vascular resistance,and pulmonary arterial pressure,culminating in right heart failure and premature mortality.Decades of research have yielded significant strides in comprehending the molecular mechanisms involved in pulmonary vascular remodeling and PH,enabling the development of targeting drugs and clinical diagnosis optimization.Nevertheless,PH remains a complicated clinical syndrome with non-specific manifestations.Meanwhile,the existing drugs are not universally effective,being able to mitigate only clinical symptoms,but fail to preventing or reversing pathological vascular remodeling progress.Hence,the identification of new diagnostic markers and intervention targets remains paramount to diminish misdiagnosis and advance precision medicine.Epigenetic modifications play a pivotal role in pulmonary vascular remodeling and PH pathogenesis.RNA methylation,a reversible chemical modification of RNA,has recently gained much attention from researchers,demonstrating significant roles in the onset and progression of PH.This encompasses phenotypic switch of smooth muscle cells,dysfunction of endothelial cells,and inflammatory responses of monocytes/macrophages.Gene ablation of RNA methylation modulators in SuHx(SU5416+Hypoxia)mice shows reduced pulmonary vascular remodeling and improved hemodynamic parameters in vivo.Meanwhile,inhibition of RNA methylation modulators also improves the proliferation of vascular cells and activation of macrophages in vitro.In addition,numerous studies have underscored abnormal metabolic reprogramming as a universal hallmark of PH,such as increased glucose uptake,glycolysis,fatty acid oxidation,and glutamate metabolism.All these dysfunctions of metabolic reprogramming in various vascular and perivascular cells can exacerbate pulmonary vascular remodeling.Of note,a large number of studies have shown that inhibition of metabolic reprogramming could also reverse ri

关 键 词：肺动脉高压 血管重构 RNA甲基化 代谢重编程 

分 类 号：R544.1[医药卫生—心血管疾病]