MicroRNAs in the progression of atherosclerosis: rise and fall of the atherosclerotic plaque

MicroRNAs in atherosclerosis progression

Andrea Rampin
Laboratory of Cardiovascular Pathophysiology and Regenerative Medicine, IRCCS MultiMedica, Milan, Italy
Martina Mutoli
Laboratory of Cardiovascular Pathophysiology and Regenerative Medicine, IRCCS MultiMedica, Milan, Italy
Massimiliano Martelli
Division of Vascular Surgery, IRCCS MultiMedica, Milan, Italy
Alberto M. Settembrini
Division of Vascular Surgery, IRCCS MultiMedica, Milan, Italy
Fabio Martelli
Molecular Cardiology Laboratory, IRCCS Policlinico San Donato, Milan, Italy
Tijana Mitić
University/British Heart Foundation Centre for Cardiovascular Science, Queen's Medical Research Institute (QMRI), The University of Edinburgh, Edinburgh, UK
Miron Sopić
Cardiovascular Research Unit, Department of Precision Health, Luxembourg Institute of Health, Rue Thomas Edison, Strassen, Luxembourg; Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, Belgrade, Serbia.
Antonino Bruno
Laboratory of Innate Immunity, Unit of Molecular Pathology, Biochemistry and Immunology, IRCCS MultiMedica, Milan, Italy; Laboratory of Immunology and General Pathology, Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy; Centro di Ricerca per l'Invecchiamento di Successo (CRIS), University of Insubria, Varese, Italy
Gaia Spinetti
Laboratory of Cardiovascular Pathophysiology and Regenerative Medicine, IRCCS MultiMedica, Milan, Italy

Abstract

Atherosclerosis is the main cause of mortality globally, being at the basis of most cardiovascular diseases. It is a multifactorial disease, arising from complex interactions comprising changes in lipid metabolism, inflammation and oxidative stress. These factors contribute to endothelial damage and dysfunction, the accumulation of immune cells and smooth muscle cells in the intima, ultimately leading to the formation of atherosclerotic plaques, which restricts blood flow through the vessels. Much progress has been made in the last decades in debunking the underlying mechanisms of atherosclerosis development, especially concerning the evaluation and prediction of plaque stability and the understanding of the roles played by each of the involved cell types. As yet, mechanisms that drive plaque development toward specific 'vulnerable' phenotypes remain undiscovered. Based on recent advancements in RNA therapeutics, this review aims to illustrate a comprehensive overview of miRNAs relevant to various aspects of atherosclerosis and emphasizes their theranostic potential, highlighting their dual role as both drug targets and biomarkers.

References

  1. Causes of death - standardized death rate by NUTS 2 region of residence. 2023. https://doi.org/10.2908/hlth_cd_asdr2
  2. Frostegard J. Immunity, atherosclerosis and cardiovascular disease. BMC Med 2013; 11:117. https://doi.org/10.1186/1741-7015-11-117
  3. de Weerd M, Greving JP, Hedblad B, et al. Prevalence of asymptomatic carotid artery stenosis in the general population: an individual participant data meta-analysis. Stroke 2010; 41:1294-7. https://doi.org/10.1161/STROKEAHA.110.581058
  4. Sanchez-Ruderisch H, Queiros AM, Fliegner D, et al. Sex-specific regulation of cardiac microRNAs targeting mitochondrial proteins in pressure overload. Biol Sex Differ 2019; 10:8. https://doi.org/10.1186/s13293-019-0222-1
  5. Lu C, Donners M, Karel J, et al. Sex-specific differences in cytokine signaling pathways in circulating monocytes of cardiovascular disease patients. Atherosclerosis 2023; 384:117123. https://doi.org/10.1016/j.atherosclerosis.2023.04.005
  6. Wahid F, Shehzad A, Khan T, Kim YY. MicroRNAs: synthesis, mechanism, function, and recent clinical trials. Biochim Biophys Acta 2010; 1803:1231-43. https://doi.org/10.1016/j.bbamcr.2010.06.013
  7. Brandes F, Meidert AS, Kirchner B, et al. Identification of microRNA biomarkers simultaneously expressed in circulating extracellular vesicles and atherosclerotic plaques. Front Cardiovasc Med 2024; 11:1307832. https://doi.org/10.3389/fcvm.2024.1307832
  8. Chandrasekera D, Katare R. Exosomal microRNAs in diabetic heart disease. Cardiovasc Diabetol 2022; 21:122. https://doi.org/10.1186/s12933-022-01544-2
  9. Yamaguchi T, Morino K. Perivascular mechanical environment: A narrative review of the role of externally applied mechanical force in the pathogenesis of atherosclerosis. Front Cardiovasc Med 2022; 9:944356. https://doi.org/10.3389/fcvm.2022.944356
  10. Libby P, Buring JE, Badimon L, et al. Atherosclerosis. Nat Rev Dis Primers 2019; 5:56. https://doi.org/10.1038/s41572-019-0106-z
  11. Carnevale R, Bartimoccia S, Nocella C, et al. LDL oxidation by platelets propagates platelet activation via an oxidative stress-mediated mechanism. Atherosclerosis 2014; 237:108-16. https://doi.org/10.1016/j.atherosclerosis.2014.08.041
  12. Zilversmit DB. Atherogenic nature of triglycerides, postprandial lipidemia, and triglyceride-rich remnant lipoproteins. Clin Chem 1995; 41:153-8. https://doi.org/10.1093/clinchem/41.1.153
  13. Pickett JR, Wu Y, Zacchi LF, Ta HT. Targeting endothelial vascular cell adhesion molecule-1 in atherosclerosis: drug discovery and development of vascular cell adhesion molecule-1-directed novel therapeutics. Cardiovasc Res 2023; 119:2278-93. https://doi.org/10.1093/cvr/cvad130
  14. Horkko S, Binder CJ, Shaw PX, et al. Immunological responses to oxidized LDL. Free Radic Biol Med 2000; 28:1771-9. https://doi.org/10.1016/s0891-5849(00)00333-6
  15. Kruth HS, Jones NL, Huang W, et al. Macropinocytosis is the endocytic pathway that mediates macrophage foam cell formation with native low density lipoprotein. J Biol Chem 2005; 280:2352-60. https://doi.org/10.1074/jbc.M407167200
  16. Costet P, Luo Y, Wang N, Tall AR. Sterol-dependent transactivation of the ABC1 promoter by the liver X receptor/retinoid X receptor. J Biol Chem 2000; 275:28240-5. https://doi.org/10.1074/jbc.M003337200
  17. Xu Y, Liu C, Han X, et al. E17241 as a Novel ABCA1 (ATP-Binding Cassette Transporter A1) Upregulator Ameliorates Atherosclerosis in Mice. Arterioscler Thromb Vasc Biol 2021; 41:e284-e98. https://doi.org/10.1161/ATVBAHA.120.314156
  18. Qian Z, Zhao Y, Wan C, et al. Pyroptosis in the Initiation and Progression of Atherosclerosis. Front Pharmacol 2021; 12:652963. https://doi.org/10.3389/fphar.2021.652963
  19. Hurt-Camejo E, Camejo G. ApoB-100 Lipoprotein Complex Formation with Intima Proteoglycans as a Cause of Atherosclerosis and Its Possible Ex Vivo Evaluation as a Disease Biomarker. J Cardiovasc Dev Dis 2018; 5:36. https://doi.org/10.3390/jcdd5030036
  20. Vekic J, Zeljkovic A, Cicero AFG, et al. Atherosclerosis Development and Progression: The Role of Atherogenic Small, Dense LDL. Medicina (Kaunas) 2022; 58:299. https://doi.org/10.3390/medicina58020299
  21. Jopling C. Liver-specific microRNA-122: Biogenesis and function. RNA Biol 2012; 9:137-42. https://doi.org/10.4161/rna.18827
  22. Willeit P, Skroblin P, Moschen AR, et al. Circulating MicroRNA-122 Is Associated With the Risk of New-Onset Metabolic Syndrome and Type 2 Diabetes. Diabetes 2017; 66:347-57. https://doi.org/10.2337/db16-0731
  23. Wang YL, Yu W. Association of circulating microRNA-122 with presence and severity of atherosclerotic lesions. PeerJ 2018; 6:e5218. https://doi.org/10.7717/peerj.5218
  24. Gao W, He HW, Wang ZM, et al. Plasma levels of lipometabolism-related miR-122 and miR-370 are increased in patients with hyperlipidemia and associated with coronary artery disease. Lipids Health Dis 2012; 11:55. https://doi.org/10.1186/1476-511X-11-55
  25. Tsai WC, Hsu SD, Hsu CS, et al. MicroRNA-122 plays a critical role in liver homeostasis and hepatocarcinogenesis. J Clin Invest 2012; 122:2884-97. https://doi.org/10.1172/JCI63455
  26. Esau C, Davis S, Murray SF, et al. miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metab 2006; 3:87-98. https://doi.org/10.1016/j.cmet.2006.01.005
  27. Rohlenova K, Veys K, Miranda-Santos I, et al. Endothelial Cell Metabolism in Health and Disease. Trends Cell Biol 2018; 28:224-36. https://doi.org/10.1016/j.tcb.2017.10.010
  28. Rotllan N, Price N, Pati P, et al. microRNAs in lipoprotein metabolism and cardiometabolic disorders. Atherosclerosis 2016; 246:352-60. https://doi.org/10.1016/j.atherosclerosis.2016.01.025
  29. Hsu SH, Wang B, Kota J, et al. Essential metabolic, anti-inflammatory, and anti-tumorigenic functions of miR-122 in liver. J Clin Invest 2012; 122:2871-83. https://doi.org/10.1172/JCI63539
  30. Fernandez-Tussy P, Ruz-Maldonado I, Fernandez-Hernando C. MicroRNAs and Circular RNAs in Lipoprotein Metabolism. Curr Atheroscler Rep 2021; 23:33. https://doi.org/10.1007/s11883-021-00934-3
  31. Soh J, Iqbal J, Queiroz J, et al. MicroRNA-30c reduces hyperlipidemia and atherosclerosis in mice by decreasing lipid synthesis and lipoprotein secretion. Nat Med 2013; 19:892-900. https://doi.org/10.1038/nm.3200
  32. Irani S, Hussain MM. Role of microRNA-30c in lipid metabolism, adipogenesis, cardiac remodeling and cancer. Curr Opin Lipidol 2015; 26:139-46. https://doi.org/10.1097/MOL.0000000000000162
  33. Hussain MM, Rava P, Pan X, et al. Microsomal triglyceride transfer protein in plasma and cellular lipid metabolism. Curr Opin Lipidol 2008; 19:277-84. https://doi.org/10.1097/MOL.0b013e3282feea85
  34. Ceolotto G, Giannella A, Albiero M, et al. miR-30c-5p regulates macrophage-mediated inflammation and pro-atherosclerosis pathways. Cardiovasc Res 2017; 113:1627-38. https://doi.org/10.1093/cvr/cvx157
  35. Li P, Zhong X, Li J, et al. MicroRNA-30c-5p inhibits NLRP3 inflammasome-mediated endothelial cell pyroptosis through FOXO3 down-regulation in atherosclerosis. Biochem Biophys Res Commun 2018; 503:2833-40. https://doi.org/10.1016/j.bbrc.2018.08.049
  36. Yadav PK, Haruehanroengra P, Irani S, et al. Novel efficacious microRNA-30c analogs reduce apolipoprotein B secretion in human hepatoma and primary hepatocyte cells. J Biol Chem 2022; 298:101813. https://doi.org/10.1016/j.jbc.2022.101813
  37. Kaser A, Hava DL, Dougan SK, et al. Microsomal triglyceride transfer protein regulates endogenous and exogenous antigen presentation by group 1 CD1 molecules. Eur J Immunol 2008; 38:2351-9. https://doi.org/10.1002/eji.200738102
  38. Zhao Y, Liu YS. Longevity Factor FOXO3: A Key Regulator in Aging-Related Vascular Diseases. Front Cardiovasc Med 2021; 8:778674. https://doi.org/10.3389/fcvm.2021.778674
  39. Tao R, Xiong X, DePinho RA, et al. FoxO3 transcription factor and Sirt6 deacetylase regulate low density lipoprotein (LDL)-cholesterol homeostasis via control of the proprotein convertase subtilisin/kexin type 9 (Pcsk9) gene expression. J Biol Chem 2013; 288:29252-9. https://doi.org/10.1074/jbc.M113.481473
  40. Ganjifrockwala F, Joseph J, George G. Serum Oxidized LDL Levels in Type 2 Diabetic Patients with Retinopathy in Mthatha Region of the Eastern Cape Province of South Africa. Oxid Med Cell Longev 2016; 2016:2063103. https://doi.org/10.1155/2016/2063103
  41. Goedeke L, Rotllan N, Canfran-Duque A, et al. MicroRNA-148a regulates LDL receptor and ABCA1 expression to control circulating lipoprotein levels. Nat Med 2015; 21:1280-9. https://doi.org/10.1038/nm.3949
  42. Wagschal A, Najafi-Shoushtari SH, Wang L, et al. Genome-wide identification of microRNAs regulating cholesterol and triglyceride homeostasis. Nat Med 2015; 21:1290-7. https://doi.org/10.1038/nm.3980
  43. Rotllan N, Zhang X, Canfran-Duque A, et al. Antagonism of miR-148a attenuates atherosclerosis progression in APOB(TG)Apobec(-/-)Ldlr(+/-) mice: A brief report. Biomed Pharmacother 2022; 153:113419. https://doi.org/10.1016/j.biopha.2022.113419
  44. Wang Z, Mohan R, Chen X, et al. microRNA-483 Protects Pancreatic beta-Cells by Targeting ALDH1A3. Endocrinology 2021; 162:bqab031. https://doi.org/10.1210/endocr/bqab031
  45. Dong J, He M, Li J, et al. microRNA-483 ameliorates hypercholesterolemia by inhibiting PCSK9 production. JCI Insight 2020; 5:e143812. https://doi.org/10.1172/jci.insight.143812
  46. Shapiro MD, Fazio S. PCSK9 and Atherosclerosis - Lipids and Beyond. J Atheroscler Thromb 2017; 24:462-72. https://doi.org/10.5551/jat.RV17003
  47. Lyford J. PCSK9 inhibitor evolocumab gets green light for European approval. The Pharmaceutical Journal 2015; 294. https://doi.org/10.1211/pj.2015.20068650
  48. Pecin I, Reiner Z. Alirocumab: targeting PCSK9 to treat hypercholesterolemia. Drugs Today (Barc) 2015; 51:681-7. https://doi.org/10.1358/dot.2015.51.12.2435830
  49. Lamb YN. Inclisiran: First Approval. Drugs 2021; 81:389-95. https://doi.org/10.1007/s40265-021-01473-6
  50. Wang L, Wang B, Jia L, et al. Shear stress leads to the dysfunction of endothelial cells through the Cav-1-mediated KLF2/eNOS/ERK signaling pathway under physiological conditions. Open Life Sci 2023; 18:20220587. https://doi.org/10.1515/biol-2022-0587
  51. De Nisco G, Hartman EMJ, Torta E, et al. Predicting Lipid-Rich Plaque Progression in Coronary Arteries Using Multimodal Imaging and Wall Shear Stress Signatures. Arterioscler Thromb Vasc Biol 2024; 44:976-86. https://doi.org/10.1161/ATVBAHA.123.320337
  52. Li Y, Yang N, Dong B, et al. MicroRNA-122 promotes endothelial cell apoptosis by targeting XIAP: Therapeutic implication for atherosclerosis. Life Sci 2019; 232:116590. https://doi.org/10.1016/j.lfs.2019.116590
  53. Zhao Z, Zhong L, Li P, et al. Cholesterol impairs hepatocyte lysosomal function causing M1 polarization of macrophages via exosomal miR-122-5p. Exp Cell Res 2020; 387:111738. https://doi.org/10.1016/j.yexcr.2019.111738
  54. Shah R, Ziegler O, Yeri A, et al. MicroRNAs Associated With Reverse Left Ventricular Remodeling in Humans Identify Pathways of Heart Failure Progression. Circ Heart Fail 2018; 11:e004278. https://doi.org/10.1161/CIRCHEARTFAILURE.117.004278
  55. Cengiz M, Yavuzer S, Kilickiran Avci B, et al. Circulating miR-21 and eNOS in subclinical atherosclerosis in patients with hypertension. Clin Exp Hypertens 2015; 37:643-9. https://doi.org/10.3109/10641963.2015.1036064
  56. Torres-Paz YE, Gamboa R, Fuentevilla-Alvarez G, et al. Overexpression of microRNA-21-5p and microRNA-221-5p in Monocytes Increases the Risk of Developing Coronary Artery Disease. Int J Mol Sci 2023; 24:8641. https://doi.org/10.3390/ijms24108641
  57. Yang D, Yang Z, Chen L, et al. Dihydromyricetin increases endothelial nitric oxide production and inhibits atherosclerosis through microRNA-21 in apolipoprotein E-deficient mice. J Cell Mol Med 2020; 24:5911-25. https://doi.org/10.1111/jcmm.15278
  58. Jing R, Zhong QQ, Long TY, et al. Downregulated miRNA-26a-5p induces the apoptosis of endothelial cells in coronary heart disease by inhibiting PI3K/AKT pathway. Eur Rev Med Pharmacol Sci 2019; 23:4940-7. https://doi.org/10.26355/eurrev_201906_18084
  59. de Yebenes VG, Briones AM, Martos-Folgado I, et al. Aging-Associated miR-217 Aggravates Atherosclerosis and Promotes Cardiovascular Dysfunction. Arterioscler Thromb Vasc Biol 2020; 40:2408-24. https://doi.org/10.1161/ATVBAHA.120.314333
  60. Ahluwalia PK, Pandey RK, Sehajpal PK, Prajapati VK. Perturbed microRNA Expression by Mycobacterium tuberculosis Promotes Macrophage Polarization Leading to Pro-survival Foam Cell. Front Immunol 2017; 8:107. https://doi.org/10.3389/fimmu.2017.00107
  61. Li X, Kong D, Chen H, et al. miR-155 acts as an anti-inflammatory factor in atherosclerosis-associated foam cell formation by repressing calcium-regulated heat stable protein 1. Sci Rep 2016; 6:21789. https://doi.org/10.1038/srep21789
  62. Wang G, Chen JJ, Deng WY, et al. CTRP12 ameliorates atherosclerosis by promoting cholesterol efflux and inhibiting inflammatory response via the miR-155-5p/LXRalpha pathway. Cell Death Dis 2021; 12:254. https://doi.org/10.1038/s41419-021-03544-8
  63. Tian FJ, An LN, Wang GK, et al. Elevated microRNA-155 promotes foam cell formation by targeting HBP1 in atherogenesis. Cardiovasc Res 2014; 103:100-10. https://doi.org/10.1093/cvr/cvu070
  64. Rayner KJ, Suarez Y, Davalos A, et al. MiR-33 contributes to the regulation of cholesterol homeostasis. Science 2010; 328:1570-3. https://doi.org/10.1126/science.1189862
  65. Davalos A, Goedeke L, Smibert P, et al. miR-33a/b contribute to the regulation of fatty acid metabolism and insulin signaling. Proc Natl Acad Sci U S A 2011; 108:9232-7. https://doi.org/10.1073/pnas.1102281108
  66. Gerin I, Clerbaux LA, Haumont O, et al. Expression of miR-33 from an SREBP2 intron inhibits cholesterol export and fatty acid oxidation. J Biol Chem 2010; 285:33652-61. https://doi.org/10.1074/jbc.M110.152090
  67. Liu D, Zhang M, Xie W, et al. MiR-486 regulates cholesterol efflux by targeting HAT1. Biochem Biophys Res Commun 2016; 472:418-24. https://doi.org/10.1016/j.bbrc.2015.11.128
  68. Xie W, Li L, Zhang M, et al. MicroRNA-27 Prevents Atherosclerosis by Suppressing Lipoprotein Lipase-Induced Lipid Accumulation and Inflammatory Response in Apolipoprotein E Knockout Mice. PLoS One 2016; 11:e0157085. https://doi.org/10.1371/journal.pone.0157085
  69. Chait A, Robertson HT, Brunzell JD. Chylomicronemia syndrome in diabetes mellitus. Diabetes Care 1981; 4:343-8. https://doi.org/10.2337/diacare.4.3.343
  70. Babaev VR, Patel MB, Semenkovich CF, et al. Macrophage lipoprotein lipase promotes foam cell formation and atherosclerosis in low density lipoprotein receptor-deficient mice. J Biol Chem 2000; 275:26293-9. https://doi.org/10.1074/jbc.M002423200
  71. Wei Y, Corbalan-Campos J, Gurung R, et al. Dicer in Macrophages Prevents Atherosclerosis by Promoting Mitochondrial Oxidative Metabolism. Circulation 2018; 138:2007-20. https://doi.org/10.1161/CIRCULATIONAHA.117.031589
  72. Hu YW, Hu YR, Zhao JY, et al. An agomir of miR-144-3p accelerates plaque formation through impairing reverse cholesterol transport and promoting pro-inflammatory cytokine production. PLoS One 2014; 9:e94997. https://doi.org/10.1371/journal.pone.0094997
  73. Lu X, Yang B, Yang H, et al. MicroRNA-320b Modulates Cholesterol Efflux and Atherosclerosis. J Atheroscler Thromb 2022; 29:200-20. https://doi.org/10.5551/jat.57125
  74. He PP, Ouyang XP, Tang YY, et al. MicroRNA-590 attenuates lipid accumulation and pro-inflammatory cytokine secretion by targeting lipoprotein lipase gene in human THP-1 macrophages. Biochimie 2014; 106:81-90. https://doi.org/10.1016/j.biochi.2014.08.003
  75. Xu Y, Xu Y, Zhu Y, et al. Macrophage miR-34a Is a Key Regulator of Cholesterol Efflux and Atherosclerosis. Mol Ther 2020; 28:202-16. https://doi.org/10.1016/j.ymthe.2019.09.008
  76. Wang M, Wang D, Zhang Y, et al. Adiponectin increases macrophages cholesterol efflux and suppresses foam cell formation in patients with type 2 diabetes mellitus. Atherosclerosis 2013; 229:62-70. https://doi.org/10.1016/j.atherosclerosis.2013.01.017
  77. Li J, Zhang S. microRNA-150 inhibits the formation of macrophage foam cells through targeting adiponectin receptor 2. Biochem Biophys Res Commun 2016; 476:218-24. https://doi.org/10.1016/j.bbrc.2016.05.096
  78. Moore KJ, Tabas I. Macrophages in the pathogenesis of atherosclerosis. Cell 2011; 145:341-55. https://doi.org/10.1016/j.cell.2011.04.005
  79. Parisi L, Bassani B, Tremolati M, et al. Natural Killer Cells in the Orchestration of Chronic Inflammatory Diseases. J Immunol Res 2017; 2017:4218254. https://doi.org/10.1155/2017/4218254
  80. Knorr M, Munzel T, Wenzel P. Interplay of NK cells and monocytes in vascular inflammation and myocardial infarction. Front Physiol 2014; 5:295. https://doi.org/10.3389/fphys.2014.00295
  81. Bonaccorsi I, De Pasquale C, Campana S, et al. Natural killer cells in the innate immunity network of atherosclerosis. Immunol Lett 2015; 168:51-7. https://doi.org/10.1016/j.imlet.2015.09.006
  82. Bot I, Shi GP, Kovanen PT. Mast cells as effectors in atherosclerosis. Arterioscler Thromb Vasc Biol 2015; 35:265-71. https://doi.org/10.1161/ATVBAHA.114.303570
  83. Kovanen PT. Mast Cells as Potential Accelerators of Human Atherosclerosis-From Early to Late Lesions. Int J Mol Sci 2019; 20:4479. https://doi.org/10.3390/ijms20184479
  84. Spinas E, Kritas SK, Saggini A, et al. Role of mast cells in atherosclerosis: a classical inflammatory disease. Int J Immunopathol Pharmacol 2014; 27:517-21. https://doi.org/10.1177/039463201402700407
  85. Bot I. The Mast Cell: A Novel Actor in Cardiac Microvessel Dysfunction. Arterioscler Thromb Vasc Biol 2021; 41:1337-8. https://doi.org/10.1161/ATVBAHA.121.316043
  86. Smith DD, Tan X, Raveendran VV, et al. Mast cell deficiency attenuates progression of atherosclerosis and hepatic steatosis in apolipoprotein E-null mice. Am J Physiol Heart Circ Physiol 2012; 302:H2612-21. https://doi.org/10.1152/ajpheart.00879.2011
  87. Nazari-Jahantigh M, Wei Y, Noels H, et al. MicroRNA-155 promotes atherosclerosis by repressing Bcl6 in macrophages. J Clin Invest 2012; 122:4190-202. https://doi.org/10.1172/JCI61716
  88. Donners MM, Wolfs IM, Stoger LJ, et al. Hematopoietic miR155 deficiency enhances atherosclerosis and decreases plaque stability in hyperlipidemic mice. PLoS One 2012; 7:e35877. https://doi.org/10.1371/journal.pone.0035877
  89. O'Connell RM, Chaudhuri AA, Rao DS, Baltimore D. Inositol phosphatase SHIP1 is a primary target of miR-155. Proc Natl Acad Sci U S A 2009; 106:7113-8. https://doi.org/10.1073/pnas.0902636106
  90. Liu G, Friggeri A, Yang Y, et al. miR-147, a microRNA that is induced upon Toll-like receptor stimulation, regulates murine macrophage inflammatory responses. Proc Natl Acad Sci U S A 2009; 106:15819-24. https://doi.org/10.1073/pnas.0901216106
  91. Sheedy FJ, Palsson-McDermott E, Hennessy EJ, et al. Negative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miR-21. Nat Immunol 2010; 11:141-7. https://doi.org/10.1038/ni.1828
  92. Spinetti G, Sangalli E, Tagliabue E, et al. MicroRNA-21/PDCD4 Proapoptotic Signaling From Circulating CD34(+) Cells to Vascular Endothelial Cells: A Potential Contributor to Adverse Cardiovascular Outcomes in Patients With Critical Limb Ischemia. Diabetes Care 2020; 43:1520-9. https://doi.org/10.2337/dc19-2227
  93. Taganov KD, Boldin MP, Chang KJ, Baltimore D. NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci U S A 2006; 103:12481-6. https://doi.org/10.1073/pnas.0605298103
  94. Spinetti G, Mutoli M, Greco S, et al. Cardiovascular complications of diabetes: role of non-coding RNAs in the crosstalk between immune and cardiovascular systems. Cardiovasc Diabetol 2023; 22:122. https://doi.org/10.1186/s12933-023-01842-3
  95. Dai R, Phillips RA, Zhang Y, et al. Suppression of LPS-induced Interferon-gamma and nitric oxide in splenic lymphocytes by select estrogen-regulated microRNAs: a novel mechanism of immune modulation. Blood 2008; 112:4591-7. https://doi.org/10.1182/blood-2008-04-152488
  96. Mensa E, Giuliani A, Matacchione G, et al. Circulating miR-146a in healthy aging and type 2 diabetes: Age- and gender-specific trajectories. Mech Ageing Dev 2019; 180:1-10. https://doi.org/10.1016/j.mad.2019.03.001
  97. Cimato TR, Palka BA, Lang JK, Young RF. LDL cholesterol modulates human CD34+ HSPCs through effects on proliferation and the IL-17 G-CSF axis. PLoS One 2013; 8:e73861. https://doi.org/10.1371/journal.pone.0073861
  98. Eizawa T, Ikeda U, Murakami Y, et al. Decrease in circulating endothelial progenitor cells in patients with stable coronary artery disease. Heart 2004; 90:685-6. https://doi.org/10.1136/hrt.2002.008144
  99. Daub K, Langer H, Seizer P, et al. Platelets induce differentiation of human CD34+ progenitor cells into foam cells and endothelial cells. FASEB J 2006; 20:2559-61. https://doi.org/10.1096/fj.06-6265fje
  100. Chen MT, Lin HS, Shen C, et al. PU.1-Regulated Long Noncoding RNA lnc-MC Controls Human Monocyte/Macrophage Differentiation through Interaction with MicroRNA 199a-5p. Mol Cell Biol 2015; 35:3212-24. https://doi.org/10.1128/MCB.00429-15
  101. Zhang Z, Salisbury D, Sallam T. Long Noncoding RNAs in Atherosclerosis: JACC Review Topic of the Week. J Am Coll Cardiol 2018; 72:2380-90. https://doi.org/10.1016/j.jacc.2018.08.2161
  102. Stellos K, Langer H, Daub K, et al. Platelet-derived stromal cell-derived factor-1 regulates adhesion and promotes differentiation of human CD34+ cells to endothelial progenitor cells. Circulation 2008; 117:206-15. https://doi.org/10.1161/CIRCULATIONAHA.107.714691
  103. Hassanpour M, Salybekov AA, Kobayashi S, Asahara T. CD34 positive cells as endothelial progenitor cells in biology and medicine. Front Cell Dev Biol 2023; 11:1128134. https://doi.org/10.3389/fcell.2023.1128134
  104. Fadini GP, Albiero M. Impaired Hematopoietic Stem/Progenitor Cell Traffic and Multi-organ Damage in Diabetes. Stem Cells 2022; 40:716-23. https://doi.org/10.1093/stmcls/sxac035
  105. Templin C, Volkmann J, Emmert MY, et al. Increased Proangiogenic Activity of Mobilized CD34+ Progenitor Cells of Patients With Acute ST-Segment-Elevation Myocardial Infarction: Role of Differential MicroRNA-378 Expression. Arterioscler Thromb Vasc Biol 2017; 37:341-9. https://doi.org/10.1161/ATVBAHA.116.308695
  106. Fadini GP, Miorin M, Facco M, et al. Circulating endothelial progenitor cells are reduced in peripheral vascular complications of type 2 diabetes mellitus. J Am Coll Cardiol 2005; 45:1449-57. https://doi.org/10.1016/j.jacc.2004.11.067
  107. Spinetti G, Cordella D, Fortunato O, et al. Global remodeling of the vascular stem cell niche in bone marrow of diabetic patients: implication of the microRNA-155/FOXO3a signaling pathway. Circ Res 2013; 112:510-22. https://doi.org/10.1161/CIRCRESAHA.112.300598
  108. Spinetti G, Fortunato O, Caporali A, et al. MicroRNA-15a and microRNA-16 impair human circulating proangiogenic cell functions and are increased in the proangiogenic cells and serum of patients with critical limb ischemia. Circ Res 2013; 112:335-46. https://doi.org/10.1161/CIRCRESAHA.111.300418
  109. Chappell J, Harman JL, Narasimhan VM, et al. Extensive Proliferation of a Subset of Differentiated, yet Plastic, Medial Vascular Smooth Muscle Cells Contributes to Neointimal Formation in Mouse Injury and Atherosclerosis Models. Circ Res 2016; 119:1313-23. https://doi.org/10.1161/CIRCRESAHA.116.309799
  110. Liu M, Gomez D. Smooth Muscle Cell Phenotypic Diversity. Arterioscler Thromb Vasc Biol 2019; 39:1715-23. https://doi.org/10.1161/ATVBAHA.119.312131
  111. Shankman LS, Gomez D, Cherepanova OA, et al. KLF4-dependent phenotypic modulation of smooth muscle cells has a key role in atherosclerotic plaque pathogenesis. Nat Med 2015; 21:628-37. https://doi.org/10.1038/nm.3866
  112. Chen R, McVey DG, Shen D, et al. Phenotypic Switching of Vascular Smooth Muscle Cells in Atherosclerosis. J Am Heart Assoc 2023; 12:e031121. https://doi.org/10.1161/JAHA.123.031121
  113. Wang Y, Dubland JA, Allahverdian S, et al. Smooth Muscle Cells Contribute the Majority of Foam Cells in ApoE (Apolipoprotein E)-Deficient Mouse Atherosclerosis. Arterioscler Thromb Vasc Biol 2019; 39:876-87. https://doi.org/10.1161/ATVBAHA.119.312434
  114. Basatemur GL, Jorgensen HF, Clarke MCH, et al. Vascular smooth muscle cells in atherosclerosis. Nat Rev Cardiol 2019; 16:727-44. https://doi.org/10.1038/s41569-019-0227-9
  115. Rykaczewska U, Zhao Q, Saliba-Gustafsson P, et al. Plaque Evaluation by Ultrasound and Transcriptomics Reveals BCLAF1 as a Regulator of Smooth Muscle Cell Lipid Transdifferentiation in Atherosclerosis. Arterioscler Thromb Vasc Biol 2022; 42:659-76. https://doi.org/10.1161/ATVBAHA.121.317018
  116. Dell'Aversana C, Giorgio C, D'Amato L, et al. miR-194-5p/BCLAF1 deregulation in AML tumorigenesis. Leukemia 2017; 31:2315-25. https://doi.org/10.1038/leu.2017.64
  117. Zhang H, Wang Y, Bian X, Yin H. MicroRNA-194 acts as a suppressor during abdominal aortic aneurysm via inhibition of KDM3A-mediated BNIP3. Life Sci 2021; 277:119309. https://doi.org/10.1016/j.lfs.2021.119309
  118. Qu F, Cao P. Long noncoding RNA SOX2OT contributes to gastric cancer progression by sponging miR-194-5p from AKT2. Exp Cell Res 2018; 369:187-96. https://doi.org/10.1016/j.yexcr.2018.05.017
  119. Lin H, You B, Lin X, et al. Silencing of long non-coding RNA Sox2ot inhibits oxidative stress and inflammation of vascular smooth muscle cells in abdominal aortic aneurysm via microRNA-145-mediated Egr1 inhibition. Aging (Albany NY) 2020; 12:12684-702. https://doi.org/10.18632/aging.103077
  120. Cheng Y, Liu X, Yang J, et al. MicroRNA-145, a novel smooth muscle cell phenotypic marker and modulator, controls vascular neointimal lesion formation. Circ Res 2009; 105:158-66. https://doi.org/10.1161/CIRCRESAHA.109.197517
  121. Cordes KR, Sheehy NT, White MP, et al. miR-145 and miR-143 regulate smooth muscle cell fate and plasticity. Nature 2009; 460:705-10. https://doi.org/10.1038/nature08195
  122. Yamaguchi S, Yamahara K, Homma K, et al. The role of microRNA-145 in human embryonic stem cell differentiation into vascular cells. Atherosclerosis 2011; 219:468-74. https://doi.org/10.1016/j.atherosclerosis.2011.09.004
  123. He M, Wu N, Leong MC, et al. miR-145 improves metabolic inflammatory disease through multiple pathways. J Mol Cell Biol 2020; 12:152-62. https://doi.org/10.1093/jmcb/mjz015
  124. Gorabi AM, Kiaie N, Khosrojerdi A, et al. Implications for the role of lipopolysaccharide in the development of atherosclerosis. Trends Cardiovasc Med 2022; 32:525-33. https://doi.org/10.1016/j.tcm.2021.08.015
  125. Jiang D, Yang Y, Li D. Lipopolysaccharide induced vascular smooth muscle cells proliferation: A new potential therapeutic target for proliferative vascular diseases. Cell Prolif 2017; 50:e12332. https://doi.org/10.1111/cpr.12332
  126. de La Serre CB, Ellis CL, Lee J, et al. Propensity to high-fat diet-induced obesity in rats is associated with changes in the gut microbiota and gut inflammation. Am J Physiol Gastrointest Liver Physiol 2010; 299:G440-8. https://doi.org/10.1152/ajpgi.00098.2010
  127. Vreugdenhil AC, Snoek AM, van 't Veer C, et al. LPS-binding protein circulates in association with apoB-containing lipoproteins and enhances endotoxin-LDL/VLDL interaction. J Clin Invest 2001; 107:225-34. https://doi.org/10.1172/JCI10832
  128. Violi F, Cammisotto V, Bartimoccia S, et al. Gut-derived low-grade endotoxaemia, atherothrombosis and cardiovascular disease. Nat Rev Cardiol 2023; 20:24-37. https://doi.org/10.1038/s41569-022-00737-2
  129. Zhang C. MicroRNA-145 in vascular smooth muscle cell biology: a new therapeutic target for vascular disease. Cell Cycle 2009; 8:3469-73. https://doi.org/10.4161/cc.8.21.9837
  130. Chin DD, Poon C, Wang J, et al. miR-145 micelles mitigate atherosclerosis by modulating vascular smooth muscle cell phenotype. Biomaterials 2021; 273:120810. https://doi.org/10.1016/j.biomaterials.2021.120810
  131. Riches K, Alshanwani AR, Warburton P, et al. Elevated expression levels of miR-143/5 in saphenous vein smooth muscle cells from patients with Type 2 diabetes drive persistent changes in phenotype and function. J Mol Cell Cardiol 2014; 74:240-50. https://doi.org/10.1016/j.yjmcc.2014.05.018
  132. Rozhkov AN, Shchekochikhin DY, Ashikhmin YI, et al. The Profile of Circulating Blood microRNAs in Outpatients with Vulnerable and Stable Atherosclerotic Plaques: Associations with Cardiovascular Risks. Noncoding RNA 2022; 8:47. https://doi.org/10.3390/ncrna8040047
  133. Sala F, Aranda JF, Rotllan N, et al. MiR-143/145 deficiency attenuates the progression of atherosclerosis in Ldlr-/-mice. Thromb Haemost 2014; 112:796-802. https://doi.org/10.1160/TH13-11-0905
  134. Weber C, Schober A, Zernecke A. MicroRNAs in arterial remodelling, inflammation and atherosclerosis. Curr Drug Targets 2010; 11:950-6. https://doi.org/10.2174/138945010791591377
  135. Wei X, Hou X, Li J, Liu Y. miRNA-181a/b Regulates Phenotypes of Vessel Smooth Muscle Cells Through Serum Response Factor. DNA and Cell Biology 2017; 36:127-35. https://doi.org/10.1089/dna.2016.3525
  136. Pessi T, Viiri LE, Raitoharju E, et al. Interleukin-6 and microRNA profiles induced by oral bacteria in human atheroma derived and healthy smooth muscle cells. Springerplus 2015; 4:206. https://doi.org/10.1186/s40064-015-0993-8
  137. Remus EW, Lyle AN, Weiss D, et al. miR181a protects against angiotensin II-induced osteopontin expression in vascular smooth muscle cells. Atherosclerosis 2013; 228:168-74. https://doi.org/10.1016/j.atherosclerosis.2013.01.037
  138. Stefanadis C, Antoniou CK, Tsiachris D, Pietri P. Coronary Atherosclerotic Vulnerable Plaque: Current Perspectives. J Am Heart Assoc 2017; 6:e005543. https://doi.org/10.1161/JAHA.117.005543
  139. Lovren F, Pan Y, Quan A, et al. MicroRNA-145 targeted therapy reduces atherosclerosis. Circulation 2012; 126:S81-90. https://doi.org/10.1161/CIRCULATIONAHA.111.084186
  140. Han H, Yang S, Liang Y, et al. Teniposide regulates the phenotype switching of vascular smooth muscle cells in a miR-21-dependent manner. Biochem Biophys Res Commun 2018; 506:1040-6. https://doi.org/10.1016/j.bbrc.2018.10.198
  141. Alshanwani AR, Riches-Suman K, O'Regan DJ, et al. MicroRNA-21 drives the switch to a synthetic phenotype in human saphenous vein smooth muscle cells. IUBMB Life 2018; 70:649-57. https://doi.org/10.1002/iub.1751
  142. Hansson GK, Hellstrand M, Rymo L, et al. Interferon gamma inhibits both proliferation and expression of differentiation-specific alpha-smooth muscle actin in arterial smooth muscle cells. J Exp Med 1989; 170:1595-608. https://doi.org/10.1084/jem.170.5.1595
  143. Ma F, Xu S, Liu X, et al. The microRNA miR-29 controls innate and adaptive immune responses to intracellular bacterial infection by targeting interferon-gamma. Nat Immunol 2011; 12:861-9. https://doi.org/10.1038/ni.2073
  144. Boon RA, Seeger T, Heydt S, et al. MicroRNA-29 in aortic dilation: implications for aneurysm formation. Circ Res 2011; 109:1115-9. https://doi.org/10.1161/CIRCRESAHA.111.255737
  145. Di Gregoli K, Jenkins N, Salter R, et al. MicroRNA-24 regulates macrophage behavior and retards atherosclerosis. Arterioscler Thromb Vasc Biol 2014; 34:1990-2000. https://doi.org/10.1161/ATVBAHA.114.304088
  146. Eken SM, Jin H, Chernogubova E, et al. MicroRNA-210 Enhances Fibrous Cap Stability in Advanced Atherosclerotic Lesions. Circ Res 2017; 120:633-44. https://doi.org/10.1161/CIRCRESAHA.116.309318
  147. Karshovska E, Wei Y, Subramanian P, et al. HIF-1alpha (Hypoxia-Inducible Factor-1alpha) Promotes Macrophage Necroptosis by Regulating miR-210 and miR-383. Arterioscler Thromb Vasc Biol 2020; 40:583-96. https://doi.org/10.1161/ATVBAHA.119.313290
  148. Das A, Ganesh K, Khanna S, et al. Engulfment of apoptotic cells by macrophages: a role of microRNA-21 in the resolution of wound inflammation. J Immunol 2014; 192:1120-9. https://doi.org/10.4049/jimmunol.1300613
  149. Haneklaus M, Gerlic M, Kurowska-Stolarska M, et al. Cutting edge: miR-223 and EBV miR-BART15 regulate the NLRP3 inflammasome and IL-1beta production. J Immunol 2012; 189:3795-9. https://doi.org/10.4049/jimmunol.1200312
  150. Carter JV, Galbraith NJ, Yang D, et al. Blood-based microRNAs as biomarkers for the diagnosis of colorectal cancer: a systematic review and meta-analysis. Br J Cancer 2017; 116:762-74. https://doi.org/10.1038/bjc.2017.12
  151. Swarbrick S, Wragg N, Ghosh S, Stolzing A. Systematic Review of miRNA as Biomarkers in Alzheimer's Disease. Mol Neurobiol 2019; 56:6156-67. https://doi.org/10.1007/s12035-019-1500-y
  152. Xu D, Di K, Fan B, et al. MicroRNAs in extracellular vesicles: Sorting mechanisms, diagnostic value, isolation, and detection technology. Front Bioeng Biotechnol 2022; 10:948959. https://doi.org/10.3389/fbioe.2022.948959
  153. Mitchell PS, Parkin RK, Kroh EM, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A 2008; 105:10513-8. https://doi.org/10.1073/pnas.0804549105
  154. Arroyo JD, Chevillet JR, Kroh EM, et al. Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc Natl Acad Sci U S A 2011; 108:5003-8. https://doi.org/10.1073/pnas.1019055108
  155. Zhai KF, Duan H, Shi Y, et al. miRNAs from Plasma Extracellular Vesicles Are Signatory Noninvasive Prognostic Biomarkers against Atherosclerosis in LDLr(-/-)Mice. Oxid Med Cell Longev 2022; 2022:6887192. https://doi.org/10.1155/2022/6887192
  156. Xue S, Liu D, Zhu W, et al. Circulating MiR-17-5p, MiR-126-5p and MiR-145-3p Are Novel Biomarkers for Diagnosis of Acute Myocardial Infarction. Front Physiol 2019; 10:123. https://doi.org/10.3389/fphys.2019.00123
  157. The Importance of Determining the Expression Level of Various microRNAs in the Diagnosis of Atherosclerotic Plaque Instability. 2022. https://clinicaltrials.gov/study/NCT05680935
  158. Sopić M, Karaduzovic-Hadziabdic K, Kardassis D, et al. Transcriptomic research in atherosclerosis: Unravelling plaque phenotype and overcoming methodological challenges. Journal of Molecular and Cellular Cardiology Plus 2023; 6:100048. https://doi.org/10.1016/j.jmccpl.2023.100048
  159. Sopic M, Vladimirov S, Munjas J, et al. Targeting noncoding RNAs to treat atherosclerosis. Br J Pharmacol 2024; n/a. https://doi.org/10.1111/bph.16412
  160. de Gonzalo-Calvo D, Sopic M, Devaux Y, CA EU-CCA. Methodological considerations for circulating long noncoding RNA quantification. Trends Mol Med 2022; 28:616-8. https://doi.org/10.1016/j.molmed.2022.05.011

Send mail to Author


Send Cancel

Custom technologies based on your needs

  • MongoDB
  • ElasticSearch
  • Redis
  • Solr
  • Memcached