慢性病防治专栏

棕榈酰化促进血管衰老相关心血管疾病的研究进展

  • 吴诗亲 ,
  • 杨简 ,
  • 黄萃园 ,
  • 刘丽 ,
  • 李文强 ,
  • 王伟 ,
  • 张静
展开
  • 1.三峡大学第一临床医学院&宜昌市中心人民医院,心血管内科,(湖北 宜昌 443002 )
    2.三峡大学第一临床医学院&宜昌市中心人民医院,中心实验室,(湖北 宜昌 443002 )
    3.缺血性心血管病湖北省重点实验室 (湖北 宜昌 443002 )
    4.湖北省缺血性心血管疾病临床医学研究中心 (湖北 宜昌 443002 )

收稿日期: 2025-08-21

  网络出版日期: 2026-04-29

基金资助

国家自然科学基金项目(82170418);国家自然科学基金项目(82271618);国家自然科学基金项目(82471616);湖北省自然科学基金创新群体项目(2022CFA015);中央引导地方科技发展专项(2022BGE237);湖北省重点研发计划(2023BCB139);湖北省区域科技创新计划项目(2025EIA015);湖北省科技创新平台项目(2025CCB016);湖北省科技创新平台项目(2025CSA107)

Research progress of palmitoylation promoting vascular aging-related cardiovascular diseases

  • Shiqin WU ,
  • Jian YANG ,
  • Cuiyuan HUANG ,
  • Li LIU ,
  • Wenqiang LI ,
  • Wei WANG ,
  • Jing ZHANG
Expand
  • 1.Department of Cardiology,the First College of Clinical Medical Science,China Three Gorges University & Yichang Central People's Hospital,Yichang 443002,Hubei,Chin
    2Central Laboratory,the First College of Clinical Medical Science,China Three Gorges University & Yichang Central People's Hospital,Yichang 443002,Hubei,Chin
    3Hubei Key Laboratory of Ischemic Cardiovascular Disease,Yichang 443002,Hubei,Chin
    4Hubei Provincial Clinical Research Center for Ischemic Cardiovascular Disease,Yichang 443002,Hubei,China

Received date: 2025-08-21

  Online published: 2026-04-29

摘要

血管衰老是心血管疾病发生发展的关键因素,其特征表现为动脉硬度增加、血管壁重塑和内皮功能障碍等,包括高血压、动脉粥样硬化和心功能不全等疾病。棕榈酰化是一种蛋白质翻译后修饰,涉及棕榈酸的添加,在血管衰老中起关键作用。蛋白质棕榈酰化修饰通过调控血管细胞关键蛋白的膜定位、稳定性和信号转导,参与氧化应激、炎症放大、内皮屏障功能受损、平滑肌表型异常转化、自噬及蛋白稳态失衡等过程,在血管衰老进程中具调控作用。这些作用相互交织、影响着多种心血管相关疾病事件的发生发展。蛋白质的棕榈酰化在血管衰老中起着重要作用,为防治相关心血管事件提供重要策略。

本文引用格式

吴诗亲 , 杨简 , 黄萃园 , 刘丽 , 李文强 , 王伟 , 张静 . 棕榈酰化促进血管衰老相关心血管疾病的研究进展[J]. 实用医学杂志, 2026 , 42(9) : 1586 -1591 . DOI: 10.3969/j.issn.1006-5725.2026.09.013

Abstract

Vascular aging, characterized by increased arterial stiffness, vascular wall remodeling, and endothelial dysfunction, is a crucial factor in the occurrence and development of cardiovascular diseases, such as hypertension, atherosclerosis, and cardiac insufficiency. Palmitoylation, a post-translational modification of proteins that involves the addition of palmitic acid, plays a pivotal role in vascular aging. Protein palmitoylation exerts a regulatory effect on the process of vascular aging by modulating the membrane localization, stability, and signal transduction of key proteins in vascular cells, and by participating in oxidative stress, inflammation amplification, impaired endothelial barrier function, abnormal transformation of smooth muscle phenotype, autophagy, and protein homeostasis imbalance. These effects are interwoven and influence the occurrence and development of various cardiovascular-related disease events. Protein palmitoylation is of great significance in vascular aging and offers an important strategy for the prevention and treatment of related cardiovascular events.

参考文献

[1] 刘明波, 何新叶, 杨晓红, 等. 《中国心血管健康与疾病报告2024》要点解读[J]. 中国心血管杂志, 2025, 30(4): 384-399. doi:10.3969/j.issn.1007-5410.2025.04.006 .
[2] KASAL D A, SENA V, HUGUENIN G V B, et al. Microvascular endothelial dysfunction in vascular senescence and disease[J]. Front Cardiovasc Med, 2025, 12: 1505516. doi:10.3389/fcvm.2025.1505516 .
[3] LI M, ZHANG L, CHEN C W. Diverse roles of protein palmitoylation in cancer progression, immunity, stemness, and beyond[J]. Cells, 2023, 12(18): 2209. doi:10.3390/cells12182209 .
[4] ZHOU B, HAO Q, LIANG Y, et al. Protein palmitoylation in cancer: Molecular functions and therapeutic potential[J]. Mol Oncol, 2023, 17(1): 3-26. doi:10.1002/1878-0261.13308 .
[5] QIAN Y R, ZHAO Y J, ZHANG F. Protein palmitoylation: Biological functions, disease, and therapeutic targets[J]. MedComm, 2025, 6(3): e70096. doi:10.1002/mco2.70096 .
[6] QU M, ZHOU X, WANG X, et al. Lipid-induced S-palmitoylation as a vital regulator of cell signaling and disease development[J]. Int J Biol Sci, 2021, 17(15): 4223-4237. doi:10.7150/ijbs.64046 .
[7] TAN Y, HUANG Z, JIN Y, et al. Lipid droplets sequester palmitic acid to disrupt endothelial ciliation and exacerbate atherosclerosis in male mice[J]. Nat Commun, 2024, 15(1): 8273. doi:10.1038/s41467-024-52621-x .
[8] WEI F, WANG Y, YAO J, et al. ZDHHC7-mediated S-palmitoylation of ATG16L1 facilitates LC3 lipidation and autophagosome formation[J]. Autophagy, 2024, 20(12): 2719-2737. doi:10.1080/15548627.2024.2386915 .
[9] TABATA K, IMAI K, FUKUDA K, et al. Palmitoylation of ULK1 by ZDHHC13 plays a crucial role in autophagy[J]. Nat Commun, 2024, 15(1): 7194. doi:10.1038/s41467-024-51402-w .
[10] LIN H. Protein cysteine palmitoylation in immunity and inflammation[J]. FEBS J, 2021, 288(24): 7043-7059. doi:10.1111/febs.15728 .
[11] ZHANG Q, LI J, LIU X, et al. Inhibiting CD36 palmitoylation improves cardiac function post-infarction by regulating lipid metabolic homeostasis and autophagy[J]. Nat Commun, 2025, 16(1): 6602. doi:10.1038/s41467-025-61875-y .
[12] BALDWIN T A, TEUBER J P, KUWABARA Y, et al. Palmitoylation-dependent regulation of cardiomyocyte Rac1 signaling activity and minor effects on cardiac hypertrophy[J]. J Biol Chem, 2023, 299(12): 105426. doi:10.1016/j.jbc.2023.105426 .
[13] SOMASUNDARAM I, JAIN S M, BLOT-CHABAUD M, et al. Mitochondrial dysfunction and its association with age-related disorders[J]. Front Physiol, 2024, 15: 1384966. doi:10.3389/fphys.2024.1384966 .
[14] WANG L, CAI J, ZHAO X, et al. Palmitoylation prevents sustained inflammation by limiting NLRP3 inflammasome activation through chaperone-mediated autophagy[J]. Mol Cell, 2023, 83(2): 281-297.e10. doi:10.1016/j.molcel.2022.12.002 .
[15] ZHU X, ZHANG H W, CHEN H N, et al. Perivascular adipose tissue dysfunction aggravates adventitial remodeling in obese mini pigs via NLRP3 inflammasome/IL-1 signaling pathway[J]. Acta Pharmacol Sin, 2019, 40(1): 46-54. doi:10.1038/s41401-018-0068-9 .
[16] BALASUBRAMANIAN A, HSU A Y, GHIMIRE L, et al. The palmitoylation of gasdermin D directs its membrane translocation and pore formation during pyroptosis[J]. Sci Immunol, 2024, 9(94): eadn1452. doi:10.1126/sciimmunol.adn1452 .
[17] KEMMOKU H, TAKAHASHI K, MUKAI K, et al. Single-molecule localization microscopy reveals STING clustering at the trans-Golgi network through palmitoylation-dependent accumulation of cholesterol[J]. Nat Commun, 2024, 15: 220. doi:10.1038/s41467-023-44317-5 .
[18] KIM H J, KIM H, LEE J H, et al. Toll-like receptor 4 (TLR4): New insight immune and aging[J]. Immun Ageing, 2023, 20(1): 67. doi:10.1186/s12979-023-00383-3 .
[19] LIU Y, XIANG H, XIONG W, et al. Glucolipotoxicity induces endothelial cell dysfunction by activating autophagy and inhibiting autophagic flow[J]. Diab Vasc Dis Res, 2022, 19(3): 14791641221102513. doi:10.1177/14791641221102513 .
[20] YU Y, REN Y, LI Z, et al. Myo1b promotes premature endothelial senescence and dysfunction via suppressing autophagy: Implications for vascular aging[J]. Oxid Med Cell Longev, 2023, 2023: 4654083. doi:10.1155/2023/4654083 .
[21] CHOROSZY M, ?RODA-POMIANEK K, WAWRZY?SKA M, et al. The role of palmitic acid in the co-toxicity of bacterial metabolites to endothelial cells[J]. Vasc Health Risk Manag, 2023, 19: 399-409. doi:10.2147/VHRM.S408897 .
[22] KHAN M J, RIZWAN ALAM M, WALDECK-WEIERMAIR M, et al. Inhibition of autophagy rescues palmitic acid-induced necroptosis of endothelial cells[J]. J Biol Chem, 2012, 287(25): 21110-21120. doi:10.1074/jbc.M111.319129 .
[23] VILLADANGOS L, SERRADOR J M. Subcellular localization guides eNOS function[J]. Int J Mol Sci, 2024, 25(24): 13402. doi:10.3390/ijms252413402 .
[24] BEARD R S, YANG X, MEEGAN J E, et al. Palmitoyl acyltransferase DHHC21 mediates endothelial dysfunction in systemic inflammatory response syndrome[J]. Nat Commun, 2016, 7: 12823. doi:10.1038/ncomms12823 .
[25] ASHKAR R, KHATTIB A, MUSA S, et al. PON1 has palmitoyl-protein thioesterase (PPT) activity, and can affect the presence of SR-B1 on the endothelial cell membrane[J]. Biofactors, 2024, 50(3): 608-618. doi:10.1002/biof.2029 .
[26] HU Y, FAN Y, ZHANG C, et al. Palmitic acid inhibits vascular smooth muscle cell switch to synthetic phenotype via upregulation of miR-22 expression[J]. Aging, 2022, 14(19): 8046-8060. doi:10.18632/aging.204334 .
[27] KRZYSTYNIAK A, GLUCHOWSKA A, PYTY? A, et al. 2-Bromopalmitate treatment attenuates senescence phenotype in human adult cells - possible role of palmitoylation[J]. Aging, 2024, 16(16): 11796-11808. doi:10.18632/aging.206080 .
[28] SHU Z, LI X, ZHANG W, et al. MG-132 activates sodium palmitate-induced autophagy in human vascular smooth muscle cells and inhibits senescence via the PI3K/AKT/mTOR axis[J]. Lipids Health Dis, 2024, 23(1): 282. doi:10.1186/s12944-024-02268-w .
[29] TERRY A R, NOGUEIRA V, RHO H, et al. CD36 maintains lipid homeostasis via selective uptake of monounsaturated fatty acids during matrix detachment and tumor progression[J]. Cell Metab, 2023, 35(11): 2060-2076.e9. doi:10.1016/j.cmet.2023.09.012 .
[30] ZHANG Y, DONG D, XU X, et al. Oxidized high-density lipoprotein promotes CD36 palmitoylation and increases lipid uptake in macrophages[J]. J Biol Chem, 2022, 298(6): 102000. doi:10.1016/j.jbc.2022.102000 .
[31] CHEN Y, YANG M, HUANG W, et al. Mitochondrial metabolic reprogramming by CD36 signaling drives macrophage inflammatory responses[J]. Circ Res, 2019, 125(12): 1087-1102. doi:10.1161/CIRCRESAHA.119.315833 .
[32] WANG X, CHENG L, FU H, et al. Endothelial-derived APT1-mediated macrophage-endothelial cell interactions participate in the development of atherosclerosis by regulating the ras/MAPK signaling pathway[J]. Life, 2022, 12(4): 551. doi:10.3390/life12040551 .
[33] YEUNG J, LI W, HOLINSTAT M. Platelet signaling and disease: Targeted therapy for thrombosis and other related diseases[J]. Pharmacol Rev, 2018, 70(3): 526-548. doi:10.1124/pr.117.014530 .
[34] SALAUN C, LOCATELLI C, ZMUDA F, et al. Accessory proteins of the zDHHC family of S-acylation enzymes[J]. J Cell Sci, 2020, 133(22): jcs251819. doi:10.1242/jcs.251819 .
[35] ALKARITHI G, DUVAL C, SHI Y, et al. Thrombus structural composition in cardiovascular disease[J]. Arterioscler Thromb Vasc Biol, 2021, 41(9): 2370-2383. doi:10.1161/ATVBAHA.120.315754 .
[36] 杨乔西, 蔡军. 高血压的诊治进展[J]. 巴楚医学, 2023, 6(3): 1-11. doi:10.3969/j.issn.2096-6113.2023.03.001 .
[37] HAO W, SHAN W, WAN F, et al. Canagliflozin delays aging of HUVECs induced by palmitic acid via the ROS/p38/JNK pathway[J]. Antioxidants, 2023, 12(4): 838. doi:10.3390/antiox12040838 .
[38] MUTCHLER S M, KIRABO A, KLEYMAN T R. Epithelial sodium channel and salt-sensitive hypertension[J]. Hypertension, 2021, 77(3): 759-767. doi:10.1161/HYPERTENSIONAHA.120.14481 .
[39] NICKERSON A J, MUTCHLER S M, SHENG S, et al. Mice lacking γENaC palmitoylation sites maintain benzamil-sensitive Na+ transport despite reduced channel activity[J]. JCI Insight, 2023, 8(21): e172051. doi:10.1172/jci.insight.172051 .
[40] VELUTHAKAL R, KUMAR B, MOHAMMAD G, et al. Tiam1-Rac1 axis promotes activation of p38 MAP kinase in the development of diabetic retinopathy: Evidence for a requisite role for protein palmitoylation[J]. Cell Physiol Biochem, 2015, 36(1): 208-220. doi:10.1159/000374065 .
[41] XING X, WANG H, NIU T, et al. RUNX1 can mediate the glucose and O-GlcNAc-driven proliferation and migration of human retinal microvascular endothelial cells[J]. BMJ Open Diabetes Res Care, 2021, 9(1): e001898. doi:10.1136/bmjdrc-2020-001898 .
[42] ZHOU Y, YUE S, LI L, et al. SMPDL3B is palmitoylated and stabilized by ZDHHC5, and its silencing aggravates diabetic retinopathy of db/db mice: Activation of NLRP3/NF-κB pathway[J]. Cell Signal, 2024, 116: 111064. doi:10.1016/j.cellsig.2024.111064 .
[43] MA Y, YUAN X, WEI A, et al. Enhancing Gpx1 palmitoylation to inhibit angiogenesis by targeting PPT1[J]. Redox Biol, 2024, 77: 103376. doi:10.1016/j.redox.2024.103376 .
文章导航

/