• This record comes from PubMed

Involvement of circulating microRNAs in the pathogenesis of atherosclerosis in young patients with obesity

. 2024 Dec 31 ; 73 (S3) : S755-S769.

Language English Country Czech Republic Media print

Document type Journal Article

Obesity is considered an important factor contributing to the development of atherosclerosis. Inflammation plays a key role in endothelial dysfunction (ED), an initial stage of the atherosclerotic process. Several microRNAs (miRNAs) may play an important role in the inflammatory process, but there is a lack of information about their participation in the early stages of atherosclerosis development in patients with obesity. We aimed to assess the relations between plasma concentration of selected miRNAs, ED evaluated by reactive hyperemia index (RHI), inflammatory markers and other factors involved in the pathogenesis of atherosclerosis in adolescents and young adults with obesity. Participants (30 males, 30 females; aged 15 25 years) were divided into two groups: those with overweight/obesity (OW/O) (20 males, 20 females) and controls (C) (10 males, 10 females). The plasma concentrations of inflammatory markers, cytokines, adipocytokines, markers of lipid profile and glucose metabolism and selected miRNAs (miR 92, 126, -146a, -155) were analyzed. No significant differences in any of the miRNAs were found between the groups. MiR-146a correlated positively with RHI. Dividing the group by sex showed more significant associations between miRNA and analyzed parameters (IL-6, fasting glycemia) in men. Several observed correlations indicate a potential role of miRNAs in inflammation, the atherosclerotic process and glycemic control, primarily in male subjects with obesity. The relatively low number of observed associations between assessed parameters related to obesity and the pathogenesis of its complications could be attributed to the early stage of the atherosclerotic process in young subjects with obesity, where only subtle abnormalities are expectedly found. Key words Endothelial dysfunction, Atherosclerosis, Obesity, MicroRNA, Reactive hyperemia index.

See more in PubMed

Martin-Rodriguez E, Guillen-Grima F, Martí A, Brugos-Larumbe A. Comorbidity associated with obesity in a large population. The APNA study. Obes Res Clin Pract. 2015;9:435–447. doi: 10.1016/j.orcp.2015.04.003. PubMed DOI

Kwaifa IK, Bahari H, Yong YK, Noor SM. Endothelial Dysfunction in Obesity-Induced Inflammation: Molecular Mechanisms and Clinical Implications. Biomolecules. 2020;10:291. doi: 10.3390/biom10020291. PubMed DOI PMC

Holvoet P, Collen D. Oxidized lipoproteins in atherosclerosis and thrombosis. FASEB J. 1994;8:1279–1284. doi: 10.1096/fasebj.8.15.8001740. PubMed DOI

Higashi Y. Roles of Oxidative Stress and Inflammation in Vascular Endothelial Dysfunction-Related Disease. Antioxidants. 2022;11:1958. doi: 10.3390/antiox11101958. PubMed DOI PMC

Shaito A, Aramouni K, Assaf R, Parenti A, Orekhov A, El Yazbi A, Pintus G, et al. Oxidative Stress-Induced Endothelial Dysfunction in Cardiovascular Diseases. Front Biosci. 2022;27:105. doi: 10.31083/j.fbl2703105. PubMed DOI

Hydbring P, Badalian-Very G. Clinical applications of microRNAs. F1000Res. 2013;2:136. doi: 10.12688/f1000research.2-136.v1. PubMed DOI PMC

Khalyfa A, Kheirandish-Gozal L, Bhattacharjee R, Khalyfa AA, Gozal D. Circulating microRNAs as Potential Biomarkers of Endothelial Dysfunction in Obese Children. Chest. 2016;149:786–800. doi: 10.1378/chest.15-0799. PubMed DOI PMC

Ait-Aissa K, Nguyen QM, Gabani M, Kassan A, Kumar S, Choi S-K, Gonzalez AA, et al. MicroRNAs and obesity-induced endothelial dysfunction: key paradigms in molecular therapy. Cardiovasc Diabetol. 2020;19:136. doi: 10.1186/s12933-020-01107-3. PubMed DOI PMC

Solly EL, Dimasi CG, Bursill CA, Psaltis PJ, Tan JTM. MicroRNAs as Therapeutic Targets and Clinical Biomarkers in Atherosclerosis. J Clin Med. 2019;8:2199. doi: 10.3390/jcm8122199. PubMed DOI PMC

Cabiati M, Fontanini M, Giacomarra M, Politano G, Randazzo E, Peroni D, Federico G, et al. Screening and Identification of Putative Long Non-Coding RNA in Childhood Obesity: Evaluation of Their Transcriptional Levels. Biomedicines. 2022;10:529. doi: 10.3390/biomedicines10030529. PubMed DOI PMC

Cole TJ, Bellizzi MC, Flegal KM, Dietz WH. Establishing a standard definition for child overweight and obesity worldwide: International survey. Br Med J. 2000;320:1–6. doi: 10.1136/bmj.320.7244.1240. PubMed DOI PMC

Karelis AD, Chamberland G, Aubertin-Leheudre M, Duval C Ecological mobility in Aging and Parkinson (EMAP) group. Validation of a portable bioelectrical impedance analyzer for the assessment of body composition. Appl Physiol Nutr Metab. 2013;38:27–32. doi: 10.1139/apnm-2012-0129. PubMed DOI

Ikeda Y, Suehiro T, Nakamura T, Kumon Y, Hashimoto K. Clinical significance of the insulin resistance index as assessed by homeostasis model assessment. Endocr J. 2001;48:81–86. doi: 10.1507/endocrj.48.81. PubMed DOI

Kuvin JT, Patel AR, Sliney K, Pandian NG, Sheffy J, Schnall RP, Karas RH, Udelson JE. Assessment of peripheral vascular endothelial function with finger arterial pulse wave amplitude. Am Heart J. 2003;146:168–174. doi: 10.1016/S0002-8703(03)00094-2. PubMed DOI

Loyer X, Potteaux S, Vion A-C, Guérin CL, Boulkroun S, Rautou P-E, Ramkhelawon B, et al. Inhibition of microRNA-92a prevents endothelial dysfunction and atherosclerosis in mice. Circ Res. 2014;114:434–443. doi: 10.1161/CIRCRESAHA.114.302213. PubMed DOI

Donghui T, Shuang B, Xulong L, Meng Y, Yujing G, Yujie H, Juan L, et al. Improvement of microvascular endothelial dysfunction induced by exercise and diet is associated with microRNA-126 in obese adolescents. Microvasc Res. 2019;123:86–91. doi: 10.1016/j.mvr.2018.10.009. PubMed DOI

Srivastava A, Nikamo P, Lohcharoenkal W, Li D, Meisgen F, Landén NX, Ståhle M, et al. MicroRNA-146a suppresses IL-17-mediated skin inflammation and is genetically associated with psoriasis. J Allergy Clin Immunol. 2017;139:550–561. doi: 10.1016/j.jaci.2016.07.025. PubMed DOI

Karkeni E, Astier J, Tourniaire F, El Abed M, Romier B, Gouranton E, Wan L, et al. Obesity-associated inflammation induces microRNA-155 expression in adipocytes and adipose tissue: outcome on adipocyte function. J Clin Endocrinol Metab. 2016;101:1615e26. doi: 10.1210/jc.2015-3410. PubMed DOI PMC

Hijmans JG, Diehl KJ, Bammert TD, Kavlich PJ, Lincenberg GM, Greiner JJ, Stauffer BL, DeSouza CA. Influence of Overweight and Obesity on Circulating Inflammation-Related microRNA. Microrna. 2018;7:148–154. doi: 10.2174/2211536607666180402120806. PubMed DOI

Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, Speleman F. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control miRNAs. Genome Biol. 2002;3:RESEARCH0034. doi: 10.1186/gb-2002-3-7-research0034. PubMed DOI PMC

Witvrouwen I, Gevaert AB, Van Craenenbroeck EM, Van Craenenbroeck AH. MicroRNA Isolation from Plasma for Real-Time qPCR Array. Curr Protoc Hum Genet. 2018;99:e69. doi: 10.1002/cphg.69. PubMed DOI

Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 2001;25:402–408. doi: 10.1006/meth.2001.1262. PubMed DOI

Gupta AK, Ravussin E, Johannsen DL, Stull AJ, Cefalu WT, Johnson WD. Endothelial Dysfunction: An Early Cardiovascular Risk Marker in Asymptomatic Obese Individuals with Prediabetes. Br J Med Res. 2012;2:413–423. doi: 10.9734/BJMMR/2012/1479. PubMed DOI PMC

Kurose S, Tsutsumi H, Yamanaka Y, Shinno H, Miyauchi T, Tamanoi A, Imai M, et al. Improvement in endothelial function by lifestyle modification focused on exercise training is associated with insulin resistance in obese patients. Obes Res Clin Pract. 2014;8:e106–e114. doi: 10.1016/j.orcp.2012.10.005. PubMed DOI

Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, Lloyd JK, et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet. 1992;340:1111–1115. doi: 10.1016/0140-6736(92)93147-F. PubMed DOI

Kuvin JT, Patel AR, Sliney K, Pandian NG, Sheffy J, Schnall RP, Karas RH, Udelson JE. Assessment of peripheral vascular endothelial function with finger arterial pulse wave amplitude. Am Heart J. 2003;146:168–174. doi: 10.1016/S0002-8703(03)00094-2. PubMed DOI

Wilk G, Osmenda G, Matusik P, Nowakowski D, Jasiewicz-Honkisz B, Ignacak A, Cześnikiewicz-Guzik M, Guzik TJ. Endothelial function assessment in atherosclerosis: comparison of brachial artery flow-mediated vasodilation and peripheral arterial tonometry. Pol Arch Med Wewn. 2013;123:443–452. doi: 10.20452/pamw.1879. PubMed DOI

Pareyn A, Allegaert K, Verhamme P, Vinckx J, Casteels K. Impaired endothelial function in adolescents with overweight or obesity measured by peripheral artery tonometzry. Pediatr Diabetes. 2015;16:98–103. doi: 10.1111/pedi.12139. PubMed DOI

Tomsa A, Klinepeter Bartz S, Krishnamurthy R, Bacha F. Endothelial Function in Youth: A Biomarker Moldulated by Adiposity-Related Insulin Resistance. J Pediatr. 2016;178:171–177. doi: 10.1016/j.jpeds.2016.07.025. PubMed DOI

Mueller UM, Walther C, Adam J, Fikenzer K, Erbs S, Mende M, Adams V, et al. Endothelial Function in Children and Adolescents Is Mainly Influenced by Age, Sex and Physical Activity - An Analysis of Reactive Hyperemic Peripheral Artery Tonometry. Circ J. 2017;81:717–725. doi: 10.1253/circj.CJ-16-0994. PubMed DOI

Singh R, Verma A, Aljabari S, Vaylyeva TL. Urinary biomarkers as indicator of chronic inflammation and endothelial dysfunction in obese adolescents. BMC Obes. 2017;4:2–9. doi: 10.1186/s40608-017-0148-2. PubMed DOI PMC

Olivieri F, Albertini MC, Orciani M, Ceka A, Cricca M, Procopio AD, Bonafè M. DNA damage response (DDR) and senescence: shuttled inflamma-miRNAs on the stage of inflamm-aging. Oncotarget. 2015;6:35509–35521. doi: 10.18632/oncotarget.5899. PubMed DOI PMC

Masotti A, Baldassarre A, Fabrizi M, Olivero G, Loreti MC, Giammaria P, Veroneli P, et al. Oral glucose tolerance test unravels circulating miRNAs associated with insulin resistance in obese preschoolers. Pediatr Obes. 2017;12:229–238. doi: 10.1111/ijpo.12133. PubMed DOI

Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136:215–233. doi: 10.1016/j.cell.2009.01.002. PubMed DOI PMC

Cereijo R, Taxerås SD, Piquer-Garcia I, Pellitero S, Martínez E, Tarascò J, Moreno P, et al. Elevated Levels of Circulating miR-92a Are Associated with Impaired Glucose Homeostasis in Patients with Obesity and Correlate with Metabolic Status After Bariatric Surgery. Obes Surg. 2020;30:174–179. doi: 10.1007/s11695-019-04104-y. PubMed DOI

Brandao BB, Lino M, Kahn CR. Extracellular miRNAs as Mediators of Obesity-Associated Disease. J Physiol. 2021;600:1155–1169. doi: 10.1113/JP280910. PubMed DOI PMC

Mir FA, Mall R, Iskandarani A, Ullah E, Samra TA, Cyprian F, Parray A, et al. Characteristic MicroRNAs Linked to Dysregulated Metabolic Pathways in Qatari Adult Subjects With Obesity and Metabolic Syndrome. Front Endocrinol. 2022;22:937089. doi: 10.3389/fendo.2022.937089. PubMed DOI PMC

Hao XZ, Fan HM. Identification of miRNAs as atherosclerosis biomarkers and functional role of miR-126 in atherosclerosis progression through MAPK signalling pathway. Eur Rev Med Pharmacol Sci. 2017;21:2725–2733. PubMed

Li HY, Zhao X, Liu YZ, Meng Z, Wang D, Yang F, Shi QW. Plasma MicroRNA-126-5p is associated with the complexity and severity of coronary artery disease in patients with stable angina pectoris. Cell Physiol Biochem. 2016;39:837–846. doi: 10.1159/000447794. PubMed DOI

Salvucci O, Jiang K, Gasperini P, Maric D, Zhu J, Sakakibara S, Espigol-Frigole G, Wang S, Tosato G. MicroRNA126 contributes to granulocyte colony-stimulating factor-induced hematopoietic progenitor cell mobilization by reducing the expression of vascular cell adhesion molecule 1. Haematologica. 2012;97:818–826. doi: 10.3324/haematol.2011.056945. PubMed DOI PMC

Wu Y, Song LT, Li JS, Zhu DW, Jiang SY, Deng JY. MicroRNA-126 regulates inflammatory cytokine secretion in human gingival fibroblasts under high glucose via targeting tumor necrosis factor receptor associated factor 6. J Periodontol. 2017;88:e179–e187. doi: 10.1902/jop.2017.170091. PubMed DOI

Ma F, Cao D, Liu Z, Li Y, Ouyang S, Wu J. Identification of novel circulating miRNAs biomarkers for healthy obese and lean children. BMC Endocr Disord. 2023;23:238. doi: 10.1186/s12902-023-01498-w. PubMed DOI PMC

Shi C, Zhu L, Chen X, Gu N, Chen L, Zhu L, Yang L, Pang L, Guo X, Ji C, Zhang C. IL-6 and TNF-α induced obesity-related inflammatory response through transcriptional regulation of miR-146b. J Interferon Cytokine Res. 2014;34:342–348. doi: 10.1089/jir.2013.0078. PubMed DOI PMC

Hashemi A, Soori R, Banitalebi E, Choobineh S. The Effect of Elastic Resistance Bands Training on Vascular Aging Related Serum microRNA-146 Expression and Atherosclerosis Risk Factors in Elderly Women with Osteosarcopenic Obesity: A Randomized Clinical Trial. J Diabetes. 2020;12:183–191. doi: 10.18502/ijdo.v12i4.5178. DOI

Behrooz M, Hajjarzadeh S, Kahroba H, Ostadrahimi A, Bastami M. Expression pattern of miR-193a, miR122, miR155, miR-15a, and miR146a in peripheral blood mononuclear cells of children with obesity and their relation to some metabolic and inflammatory biomarkers. BMC Pediatr. 2023;23:95. doi: 10.1186/s12887-023-03867-9. PubMed DOI PMC

Elton TS, Selemon H, Elton SM, Parinandi NL. Regulation of the MIR155 host gene in physiological and pathological processes. Gene. 2013;532:1–12. doi: 10.1016/j.gene.2012.12.009. PubMed DOI

Kutty RK, Nagineni CN, Samuel W, Vijayasarathy C, Hooks JJ, Redmond TM. Inflammatory cytokines regulate microRNA-155 expression in human retinal pigment epithelial cells by activating JAK/STAT pathway. Biochem Biophys Res Commun. 2010;402:390–395. doi: 10.1016/j.bbrc.2010.10.042. PubMed DOI PMC

Cerda A, Amaral AA, de Oliveira R, Moraes TI, Braga AA, Graciano-Saldarriaga ME, Fajardo CM, et al. Peripheral Blood miRome Identified miR-155 as Potential Biomarker of MetS and Cardiometabolic Risk in Obese Patients. Int J Mol Sci. 2021;22:1468. doi: 10.3390/ijms22031468. PubMed DOI PMC

Tryggestad JB, Thompson DM, Copeland KC, Short KR. Obese children have higher arterial elasticity without a difference in endothelial function: The role of body composition. Obesity. 2012;20:165–171. doi: 10.1038/oby.2011.309. PubMed DOI PMC

Nunez Lopez YO, Garufi G, Seyhan AA. Altered levels of circulating cytokines and microRNAs in lean and obese individuals with prediabetes and type 2 diabetes. Mol Biosyst. 2016;13:106–121. doi: 10.1039/C6MB00596A. PubMed DOI

Lefèvre N, Corazza F, Duchateau J, Desir J, Casimir G. Sex differences in inflammatory cytokines and CD99 expression following in vitro lipopolysaccharide stimulation. Shock. 2012;38:37–42. doi: 10.1097/SHK.0b013e3182571e46. PubMed DOI

Uhlemann M, Mobius-Winkler S, Fikenzer S, Adam J, Redlich M, Möhlenkamp S, Hilberg T, et al. Circulating microRNA-126 increases after different forms of endurance exercise in healthy adults. Eur J Prev Cardiol. 2014;21:484–491. doi: 10.1177/2047487312467902. PubMed DOI

Wahl P, Wehmeier UF, Jansen FJ, Kilian Y, Bloch W, Werner N, Mester J, Hilberg T. Acute effects of different exercise protocols on the circulating vascular microRNAs-16, -21, and -126 in trained subjects. Front Physiol. 2016;7:643. doi: 10.3389/fphys.2016.00643. PubMed DOI PMC

Guay C, Regazzi R. Circulating microRNAs as novel biomarkers for diabetes mellitus. Nat Rev Endocrinol. 2013;9:513–521. doi: 10.1038/nrendo.2013.86. PubMed DOI

D’Alessandra Y, Carena MC, Spazzafumo L, Martinelli F, Bassetti B, Devan P, Maggiolini S. Diagnostic potential of plasmatic MicroRNA signatures in stable and unstable angina. PLoS One. 2013;8:e80345. doi: 10.1371/journal.pone.0080345. PubMed DOI PMC

Zampetaki A, Kiechl S, Drozdov I, Willeit P, Mayr U, Prokop M, Shah A. Plasma microRNA profiling reveals loss of endothelial miR-126 and other miRNAs in type 2 diabetes. Circ Res. 2010;107:810–817. doi: 10.1161/CIRCRESAHA.110.226357. PubMed DOI

Find record

Citation metrics

Loading data ...

Archiving options

Loading data ...