The Journal of Practical Medicine >
The role of glutamine metabolic reprogramming in macrophages in cardiovascular disease
Received date: 2024-04-23
Online published: 2024-11-25
Cardiovascular disease (CVD) poses a significant public health challenge in China, with both incidence and mortality rates increasing. The role of macrophage metabolic reprogramming in CVD has garnered growing attention due to its direct connection to the pathogenesis of the disease and potential therapeutic interventions. Glutamine (GLN), a fundamental energy source for macrophages, plays a crucial role in this context. Alterations in GLN metabolism have substantial effects on macrophage phenotypic transformation, functional performance, and adaptive responses in the context of CVD. Therefore, this review aims to investigate the impact of GLN metabolic reprogramming on macrophages' contribution to the pathogenesis of CVD, specifically focusing on its involvement in atherosclerosis, myocardial infarction, and other cardiovascular conditions. Additionally, it will evaluate the potential of targeting GLN metabolic pathways as a therapeutic strategy.
Xing CHEN , Yan DENG . The role of glutamine metabolic reprogramming in macrophages in cardiovascular disease[J]. The Journal of Practical Medicine, 2024 , 40(22) : 3262 -3267 . DOI: 10.3969/j.issn.1006-5725.2024.22.024
| 1 | 刘明波,何新叶,杨晓红,等. 《中国心血管健康与疾病报告2023》要点解读[J]. 中国心血管杂志,2024,29(4):305-324. |
| 2 | YANG Y, KARAMPOOR S, MIRZAEI R, et al. The interplay between microbial metabolites and macrophages in cardiovascular diseases: A comprehensive review [J]. Int Immunopharmacol, 2023, 121. doi:10.1016/j.intimp.2023.110546 |
| 3 | JIN H R, WANG J, WANG Z J, et al. Lipid metabolic reprogramming in tumor microenvironment: From mechanisms to therapeutics [J]. J Hematol Oncol, 2023, 16(1): 103. doi:10.1186/s13045-023-01498-2 |
| 4 | JEONG H, LEE B, HAN S J, et al. Glucose metabolic reprogramming in autoimmune diseases [J]. Anim Cells Syst, 2023, 27(1): 149-158. doi:10.1080/19768354.2023.2234986 |
| 5 | DURANTE W. The Emerging Role of l-Glutamine in Cardiovascular Health and Disease [J]. Nutrients, 2019, 11(9):2092. doi:10.3390/nu11092092 |
| 6 | SHEN Y, ZHANG Y, LI W, et al. Glutamine metabolism: From proliferating cells to cardiomyocytes [J]. Metabolism, 2021, 121: 154778. doi:10.1016/j.metabol.2021.154778 |
| 7 | MATéS J M, DI PAOLA F J, CAMPOS-SANDOVAL J A, et al. Therapeutic targeting of glutaminolysis as an essential strategy to combat cancer [J]. Semi Cell Develop Biol, 2020, 98: 34-43. doi:10.1016/j.semcdb.2019.05.012 |
| 8 | DURANTE W. Glutamine Deficiency Promotes Immune and Endothelial Cell Dysfunction in COVID-19 [J]. Int J Mol Sci, 2023, 24(8):7593. doi:10.3390/ijms24087593 |
| 9 | SONG W, LI D, TAO L, et al. Solute carrier transporters: The metabolic gatekeepers of immune cells [J]. Acta Pharm Sin B, 2020, 10(1): 61-78. doi:10.1016/j.apsb.2019.12.006 |
| 10 | SCALISE M, POCHINI L, PINGITORE P, et al. Cysteine is not a substrate but a specific modulator of human ASCT2 (SLC1A5) transporter [J]. FEBS Lett, 2015, 589(23): 3617-3623. doi:10.1016/j.febslet.2015.10.011 |
| 11 | BHUTIA Y D, BABU E, RAMACHANDRAN S, et al. Amino Acid Transporters in Cancer and Their Relevance to “Glutamine Addiction”: Novel Targets for the Design of a New Class of Anticancer Drugs [J]. Cancer Res, 2015, 75(9): 1782-1788. doi:10.1158/0008-5472.can-14-3745 |
| 12 | YOO H C, PARK S J, NAM M, et al. A Variant of SLC1A5 Is a Mitochondrial Glutamine Transporter for Metabolic Reprogramming in Cancer Cells [J]. Cell Metab, 2020, 31(2): 267-83.e12. doi:10.1016/j.cmet.2019.11.020 |
| 13 | YOO H C, YU Y C, SUNG Y, et al. Glutamine reliance in cell metabolism [J]. Experi Mol Med, 2020, 52(9): 1496-1516. doi:10.1038/s12276-020-00504-8 |
| 14 | LI S, ZENG H, FAN J, et al. Glutamine metabolism in breast cancer and possible therapeutic targets [J]. Biochem Pharmacol, 2023, 210: 115464. doi:10.1016/j.bcp.2023.115464 |
| 15 | CRUZAT V, MACEDO ROGERO M, NOEL KEANE K, et al. Glutamine: Metabolism and Immune Function, Supplementation and Clinical Translation [J]. Nutrients, 2018, 10(11):1564. doi:10.3390/nu10111564 |
| 16 | SHANG M, CAPPELLESSO F, AMORIM R, et al. Macrophage-derived glutamine boosts satellite cells and muscle regeneration [J]. Nature, 2020, 587(7835): 626-631. doi:10.1038/s41586-020-2857-9 |
| 17 | PENG Y, ZHOU M, YANG H, et al. Regulatory Mechanism of M1/M2 Macrophage Polarization in the Development of Autoimmune Diseases [J]. Mediators Inflamm, 2023, 2023: 8821610. doi:10.1155/2023/8821610 |
| 18 | MENG D, YANG Q, WANG H, et al. Glutamine and asparagine activate mTORC1 independently of Rag GTPases [J]. J Biol Chem, 2020, 295(10): 2890-2899. doi:10.1074/jbc.ac119.011578 |
| 19 | 李泽桦,曾宇宏,冯丽芸,等. 氧化三甲胺促进M1型巨噬细胞极化加剧心肌梗死后心室重构[J]. 实用医学杂志,2022,38(20):2531-2537,2544. |
| 20 | 黄翔雨,申晓青, ZHOU Zheng,等. 细菌脂多糖及高迁移率族蛋白1对小鼠巨噬细胞M1/M2极化分型的影响[J]. 实用医学杂志,2018,34(6):929-932. |
| 21 | FESTUCCIA W T. Regulation of Adipocyte and Macrophage Functions by mTORC1 and 2 in Metabolic Diseases [J]. Mol Nutr Food Res, 2021, 65(1): e1900768. doi:10.1002/mnfr.201900768 |
| 22 | CORCORAN S E, O'NEILL L A. HIF1alpha and metabolic reprogramming in inflammation [J]. J Clin Invest, 2016, 126(10): 3699-3707. doi:10.1172/jci84431 |
| 23 | KARUNAKARAN D, THRUSH A B, NGUYEN M A, et al. Macrophage Mitochondrial Energy Status Regulates Cholesterol Efflux and Is Enhanced by Anti-miR33 in Atherosclerosis [J]. Circ Res, 2015, 117(3): 266-278. doi:10.1161/circresaha.117.305624 |
| 24 | 储莉,刘伏元,王烈成. 巨噬细胞极化及其在老年下肢动脉粥样硬化发生中的相关性[J]. 实用医学杂志,2015,31(6):944-947. |
| 25 | XIAO Q, HOU R, XIE L, et al. Macrophage metabolic reprogramming and atherosclerotic plaque microenvironment: Fostering each other?[J]. Clin Transl Med, 2023,13(5):e1257. doi:10.1002/ctm2.1257 |
| 26 | ROM O, GRAJEDA-IGLESIAS C, NAJJAR M, et al. Atherogenicity of amino acids in the lipid-laden macrophage model system in vitro and in atherosclerotic mice: A key role for triglyceride metabolism [J]. J Nutr Biochem, 2017, 45: 24-38. doi:10.1016/j.jnutbio.2017.02.023 |
| 27 | ZHANG H, WANG C, SUN H, et al. Glutamine supplementation alleviated aortic atherosclerosis in mice model and in vitro [J]. Proteomics, 2024, 24(5): e2300179. doi:10.1002/pmic.202300179 |
| 28 | PARK D, HAN C Z, ELLIOTT M R, et al. Continued clearance of apoptotic cells critically depends on the phagocyte Ucp2 protein [J]. Nature, 2011, 477(7363): 220-224. doi:10.1038/nature10340 |
| 29 | MORIOKA S, PERRY J S A, RAYMOND M H, et al. Efferocytosis induces a novel SLC program to promote glucose uptake and lactate release [J]. Nature, 2018, 563(7733): 714-718. doi:10.1038/s41586-018-0735-5 |
| 30 | TABAS I, BORNFELDT K E. Intracellular and Intercellular Aspects of Macrophage Immunometabolism in Atherosclerosis [J]. Circ Res, 2020, 126(9): 1209-1227. doi:10.1161/circresaha.119.315939 |
| 31 | FREEMERMAN A J, JOHNSON A R, SACKS G N, et al. Metabolic reprogramming of macrophages: Glucose transporter 1 (GLUT1)-mediated glucose metabolism drives a proinflammatory phenotype [J]. J Biol Chem, 2014, 289(11): 7884-9786. doi:10.1074/jbc.m113.522037 |
| 32 | FUKUZUMI M, SHINOMIYA H, SHIMIZU Y, et al. Endotoxin-induced enhancement of glucose influx into murine peritoneal macrophages via GLUT1 [J]. Infect Imm, 2016, 64(1): 108-112. |
| 33 | VATS D, MUKUNDAN L, ODEGAARD J I, et al. Oxidative metabolism and PGC-1beta attenuate macrophage-mediated inflammation [J]. Cell Metab, 2006, 4(1): 13-24. doi:10.1016/j.cmet.2006.05.011 |
| 34 | SUN X, LI Y, DENG Q, et al. Macrophage Polarization, Metabolic Reprogramming, and Inflammatory Effects in Ischemic Heart Disease [J]. Front Immunol, 2022, 13: 934040. doi:10.3389/fimmu.2022.934040 |
| 35 | YAKUPOVA E I, MALEEV G V, KRIVTSOV A V, et al. Macrophage polarization in hypoxia and ischemia/reperfusion: Insights into the role of energetic metabolism [J]. Exp Biol Med (Maywood, NJ), 2022, 247(11): 958-971. doi:10.1177/15353702221080130 |
| 36 | ZHANG Y. The essential role of glutamine metabolism in diabetic cardiomyopathy: A review [J]. Medicine (Baltimore), 2023, 102(47): e36299. doi:10.1097/md.0000000000036299 |
| 37 | NIZAMUTDINOVA I T, GULERIA R S, SINGH A B, et al. Retinoic acid protects cardiomyocytes from high glucose‐induced apoptosis through inhibition of NF‐κB signaling Pathway [J]. J Cell Physiol, 2012, 228(2): 380-392. doi:10.1002/jcp.24142 |
| 38 | PAN Y, WANG Y, ZHAO Y, et al. Inhibition of JNK phosphorylation by a novel curcumin analog prevents high glucose-induced inflammation and apoptosis in cardiomyocytes and the development of diabetic cardiomyopathy [J]. Diabetes, 2014, 63(10): 3497-511. doi:10.2337/db13-1577 |
| 39 | MENG L, LIN H, HUANG X, et al. METTL14 suppresses pyroptosis and diabetic cardiomyopathy by downregulating TINCR lncRNA [J]. Cell Death Dis, 2022, 13(1): 38. doi:10.1038/s41419-021-04484-z |
| 40 | ZHAO R X, LI W J, LU Y R, et al. Increased peripheral proinflammatory T helper subsets contribute to cardiovascular complications in diabetic patients [J]. Mediators Inflamm, 2014, 2014: 596967. doi:10.1155/2014/596967 |
| 41 | DU S, SHI H, XIONG L, et al. Canagliflozin mitigates ferroptosis and improves myocardial oxidative stress in mice with diabetic cardiomyopathy [J]. Frontiers Endocrinol, 2022, 13. doi:10.3389/fendo.2022.1011669 |
| 42 | GAO M, MONIAN P, QUADRI N, et al. Glutaminolysis and Transferrin Regulate Ferroptosis [J]. Molecular Cell, 2015, 59(2): 298-308. doi:10.1016/j.molcel.2015.06.011 |
| 43 | ZHANG M Q, WANG C C, PANG X B, et al. Role of macrophages in pulmonary arterial hypertension [J]. Frontiers Immunol, 2023, 14. doi:10.3389/fimmu.2023.1152881 |
| 44 | AL-QAZAZI R, LIMA P D A, PRISCO S Z, et al. Macrophage-NLRP3 Activation Promotes Right Ventricle Failure in Pulmonary Arterial Hypertension[J]. Am J Respir Crit Care Med,2022,206(5):608-624. doi:10.1164/rccm.202110-2274oc |
| 45 | LI M, RIDDLE S, KUMAR S, et al. Microenvironmental Regulation of Macrophage Transcriptomic and Metabolomic Profiles in Pulmonary Hypertension [J]. Front Immunol, 2021, 12: 640718. doi:10.3389/fimmu.2021.640718 |
| 46 | HE Y Y, YAN Y, JIANG X, et al. Spermine promotes pulmonary vascular remodelling and its synthase is a therapeutic target for pulmonary arterial hypertension [J]. Eur Respir J, 2020,56(5):2000522. doi:10.1183/13993003.00522-2020 |
| 47 | BERTERO T, OLDHAM W M, COTTRILL K A, et al. Vascular stiffness mechanoactivates YAP/TAZ-dependent glutaminolysis to drive pulmonary hypertension [J]. J Clin Invest, 2016, 126(9): 3313-3335. doi:10.1172/jci86387 |
| 48 | GNATCHIK R A, BRITTAIN E L, SHAH A T, et al. Dysfunctional BMPR2 signaling drives an abnormal endothelial requirement for glutamine in pulmonary arterial hypertension [J]. Pulm Circ, 2017, 7(1): 186-199. doi:10.1086/690236 |
| 49 | RYAN J J, ARCHER S L. The right ventricle in pulmonary arterial hypertension: disorders of metabolism, angiogenesis and adrenergic signaling in right ventricular failure [J]. Circulation research, 2014, 115(1): 176-188. doi:10.1161/circresaha.113.301129 |
| 50 | PIAO L, FANG Y H, PARIKH K, et al. Cardiac glutaminolysis: a maladaptive cancer metabolism pathway in the right ventricle in pulmonary hypertension [J]. J Mol Med(Berlin, Germany), 2013, 91(10): 1185-1197. doi:10.1007/s00109-013-1064-7 |
| 51 | PIRES R S, BRAGA P G S, SANTOS J M B, et al. l-Glutamine supplementation enhances glutathione peroxidase and paraoxonase-1 activities in HDL of exercising older individuals [J]. Exp Gerontol, 2021, 156: 111584. doi:10.1016/j.exger.2021.111584 |
| 52 | ZHANG X, QIN Y, WAN X, et al. Rosuvastatin exerts anti-atherosclerotic effects by improving macrophage-related foam cell formation and polarization conversion via mediating autophagic activities [J]. J Transl Med, 2021, 19(1): 62. doi:10.1186/s12967-021-02727-3 |
| 53 | NICKLIN P, BERGMAN P, ZHANG B, et al. Bidirectional transport of amino acids regulates mTOR and autophagy [J]. Cell, 2009, 136(3): 521-534. doi:10.1016/j.cell.2008.11.044 |
| 54 | JOSEPH P, GLYNN R, LONN E, et al. Rosuvastatin for the prevention of venous thromboembolism: A pooled analysis of the HOPE-3 and JUPITER randomized controlled trials [J]. Nat Cardiovasc Res, 2022, 118(3): 897-903. doi:10.1093/cvr/cvab078 |
| 55 | TIAN Z, ZHANG Y, LYU X. Promoting roles of KLF5 in myocardial infarction in mice involving microRNA-27a suppression and the following GFPT2/TGF-β/Smad2/3 axis activation [J]. Cell Cycle (Georgetown, Tex), 2021, 20(9): 874-893. doi:10.1080/15384101.2021.1907512 |
| 56 | KIM J, WANG C, DE SABANDO A R, et al. The Novel Small-Molecule SR18662 Efficiently Inhibits the Growth of Colorectal Cancer In Vitro and In Vivo [J]. Mol Cancer Ther, 2019, 18(11): 1973-1984. doi:10.1158/1535-7163.mct-18-1366 |
| 57 | TIAN Z, ZHANG Y, LYU X. Promoting roles of KLF5 in myocardial infarction in mice involving microRNA-27a suppression and the following GFPT2/TGF-beta/Smad2/3 axis activation [J]. Cell Cycle, 2021, 20(9): 874-893. doi:10.1080/15384101.2021.1907512 |
| 58 | LI J, YE Y, LIU Z, et al. Macrophage mitochondrial fission improves cancer cell phagocytosis induced by therapeutic antibodies and is impaired by glutamine competition [J]. Nat Cancer, 2022, 3(4): 453-470. doi:10.1038/s43018-022-00354-5 |
| 59 | CUI Z H, ZHANG X J, SHANG H Q, et al. Glutamine protects myocardial ischemia-reperfusion injury in rats through the PI3K/Akt signaling pathway [J]. Eur Rev Med Pharmacolog Sci, 2020, 24(1): 444-451. doi:10.23736/s0026-4725.19.05102-8 |
| 60 | SUFIT A, WEITZEL L B, HAMIEL C, et al. Pharmacologically dosed oral glutamine reduces myocardial injury in patients undergoing cardiac surgery: A randomized pilot feasibility trial [J]. JPEN J Parenter Enteral Nutri, 2012, 36(5): 556-561. doi:10.1177/0148607112448823 |
| 61 | LIU F, LI Y, LIU G. MicroRNA-200c exacerbates the ischemia/reperfusion injury of heart through targeting the glutaminase (GLS)-mediated glutamine metabolism [J]. Eur Rev Med Pharmacol Sci, 2017, 21(14): 3282-3289. |
| 62 | HE B, XIAO J, REN A J, et al. Role of miR-1 and miR-133a in myocardial ischemic postconditioning [J]. J Biomed Sci, 2011, 18(1): 22. doi:10.1186/1423-0127-18-22 |
| 63 | JIN L, ALESI G N, KANG S. Glutaminolysis as a target for cancer therapy [J]. Oncogene, 2016, 35(28): 3619-3625. doi:10.1038/onc.2015.447 |
| 64 | DELGIR S, BASTAMI M, ILKHANI K, et al. The pathways related to glutamine metabolism, glutamine inhibitors and their implication for improving the efficiency of chemotherapy in triple-negative breast cancer [J]. Mutat Res Rev Mutat Res, 2021, 787: 108366. doi:10.1016/j.mrrev.2021.108366 |
| 65 | AHLUWALIA G S, GREM J L, HAO Z, et al. Metabolism and action of amino acid analog anti-cancer agents [J]. Pharmacol Ther, 2009, 46(2): 243-271. |
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