The Emerging Role of miR-200 Family in Cardiovascular Diseases
2017; Lippincott Williams & Wilkins; Volume: 120; Issue: 9 Linguagem: Inglês
10.1161/circresaha.116.310274
ISSN1524-4571
AutoresAlessandra Magenta, Roberta Ciarapica, Maurizio C. Capogrossi,
Tópico(s)Circular RNAs in diseases
ResumoHomeCirculation ResearchVol. 120, No. 9The Emerging Role of miR-200 Family in Cardiovascular Diseases Free AccessArticle CommentaryPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessArticle CommentaryPDF/EPUBThe Emerging Role of miR-200 Family in Cardiovascular Diseases Alessandra Magenta, Roberta Ciarapica and Maurizio C. Capogrossi Alessandra MagentaAlessandra Magenta From the Istituto Dermopatico dell'Immacolata-IRCCS, FLMM, Laboratorio di Patologia Vascolare, Rome, Italy. , Roberta CiarapicaRoberta Ciarapica From the Istituto Dermopatico dell'Immacolata-IRCCS, FLMM, Laboratorio di Patologia Vascolare, Rome, Italy. and Maurizio C. CapogrossiMaurizio C. Capogrossi From the Istituto Dermopatico dell'Immacolata-IRCCS, FLMM, Laboratorio di Patologia Vascolare, Rome, Italy. Originally published28 Apr 2017https://doi.org/10.1161/CIRCRESAHA.116.310274Circulation Research. 2017;120:1399–1402Recent studies have shown that reactive oxygen species increase the expression of miR-200 family (miR-200); however, little is known about this micro-RNA family in the cardiovascular system. In this Viewpoint, we provide evidence suggesting that miR-200 may be important in conditions that affect the heart and blood vessels.Oxidative stress plays a major role in cardiovascular physiopathology and some common conditions including aging, diabetes mellitus, atherosclerosis, and reperfusion injury induce reactive oxygen species (ROS).In 2011, it was first published that endothelial and skeletal muscle cells exposed to oxidative stress, in vitro and in vivo, exhibit a marked increase in miR-2001. Subsequently, ROS ability to induce miR-200 has been confirmed in many cell types. Furthermore, hypoxia enhances miR-429, an miR-200 member, and miR-429 targets HIF-1α (hypoxia-inducible factor-1α) and decreases its expression.Most miR-200 studies have been in the cancer field: miR-200 modulates epithelial–mesenchymal transition by targeting the transcription factors ZEB1 and ZEB2 (Zinc-finger E-box binding homeobox 1 and 2) and circulating miR-200 may represent clinically useful cancer biomarkers. In contrast, the role of miR-200 in CV diseases is still poorly investigated.miR-200 and Its TargetsMiRNAs are short (21–22 nucleotides) noncoding RNAs: their seed sequence (nucleotides 2–8 from the 5′ end) targets specific mRNAs and via this mechanism they inhibit translation and also may modulate mRNA stability. The miR-200 family is composed of 5 members clustered and expressed as 2 separate polycistronic pri-miRNA transcripts: in humans, miR-200c and miR-141 are on chromosome 12; miR-200a, miR-200b, and miR-429 are on chromosome 1. They are also identified by different seed sequences: subgroup I comprises miR-141 and miR-200a; subgroup II includes miR-200b, miR-200c, and miR-429. Because each miRNA can target numerous mRNAs and the 2 miR-200 subgroups have different seed sequences, the functional impact of miR-200 can be profound. The Figure shows the major miR-200c–activated signaling pathways relevant to vascular dysfunction; other miR-200 targets are shown in the Online Table.Download figureDownload PowerPointFigure. Reactive oxygen species (ROS) upregulate miR-200c via a p53-dependent mechanism.1 MiR-200c, in turn, inhibits ZEB1 (Zinc-finger E-box binding homeobox 1) and SIRT1/endothelial nitric oxide synthase (eNOS)/forkhead box O1 (FOXO1) regulatory loop by directly targeting all of them.7 miR-200c upregulation induces growth arrest, senescence, and apoptosis. ZEB1 downregulation is implicated in all these effects; p53 is implicated in the induction of apoptosis and senescence; diminished SIRT1 expression associates with cell senescence. Moreover, miR-200c decreases nitric oxide (NO) and increases ROS production by 2 mechanisms: (1) it decreases ROS scavengers by targeting peroxiredoxin 2 (PRDX2), and forkhead box O1 (FOXO1), a transcription factor required for catalase (CAT) and manganese superoxide dismutase (MnSOD) expression; (2) it sustains ROS production via p66Shc phosphorylation in Serine 36.Notably, different miR-200 can have opposite effects on the same target: for instance, miR-200b downmodulates c-Jun protein, whereas miR-200a increases JUN by stabilizing its mRNA. Therefore, the effect of a member cannot be extended to the whole family.miR-200 and EpigeneticsA complex epigenetic circuitry modulates miR-200 expression level and contributes to its effects on gene expression.Methylation of miR-200 promoters by DNA methyltransferase 3a, inhibits miR-200 expression. In turn, miR-200c represses directly DNA methyltransferase 3a.Moreover, a strict link exists between miR-200 and histone H3 lysine 27 trimethylation, a repressive chromatin state catalyzed by Polycomb group proteins. The levels of H3 lysine 27 trimethylation result from the opposite activities of the Polycomb histone methyltransferase enhancer of zeste homolog 2 and of the histone demethylases JMJD3 and UTX. MiR-200b targets Suz12, a subunit of polycomb repressive complex 2,2 and decreases H3 lysine 27 trimethylation at the promoters of target genes leading to transcriptional derepression.JMJD3 knockdown enhances H3 lysine 27 trimethylation and downmodulates miR-200b and miR-200c expression. In keeping, enhancer of zeste homolog 2 represses miR-200b and miR-200c expression.EED (embryonic ectoderm development), another component of PCR2 (polycomb repressive complex 2), modulates transforming growth factor β–induced transcriptional repression of miR-200 genes, through the recruitment of enhancer of zeste homolog 2 methyltrasferase on their promoter. Furthermore, miR-200c targets also BMI1, a polycomb repressive complex 2 component.3In addition, miR-200 downmodulates 2 histone deacetylases: HDAC4 and Sirtuin1 (SIRT1).4Taken together, these studies suggest an antagonistic interplay between miR-200 and the epigenetic mechanisms that maintain transcriptional repression, that is, a condition usually associated with young age and low prevalence of cardiovascular diseases.5miR-200 in the Cardiovascular SystemSome conditions of cardiovascular interest that are associated with enhanced miR-200 expression; however, to date, few studies have examined miR-200 expression in vascular and myocardial cells.AgingAn age-dependent increase in oxidative stress has been reported in humans and in many animal models, and increased ROS seem to be both a consequence and a cause of aging. There is evidence that human liver exhibits an age-dependent increase of miR-200c and miR-141.6Furthermore, aging enhances miR-200c expression in human skin fibroblasts and mouse femoral artery.7Diabetes mellitus, Obesity, and Insulin ResistanceThe role of miR-200 in diabetes mellitus is complex because it acts at different levels: (1) it diminishes insulin production by inducing pancreatic β cell damage8; (2) it enhances insulin resistance via downmodulation of insulin receptor substrate-2; (3) it increases appetite by interfering with leptin signaling in the hypothalamus; (4) it has an arterial proinflammatory role: miR-200b, miR-429, and miR-200c increase in the aorta and vascular smooth muscle cells of diabetic mice and the downregulation of ZEB1 activates proinflammatory genes; (5) miR-200 has an antiangiogenic action (see below). Taken together, the above results suggest that miR-200 may contribute to diabetic vascular complications. However, there is also some evidence that miR-200 may facilitate insulin signaling: (1) miR-200 targets the transcription factor FOG2, a key protein that inhibits insulin signaling9; (2) the ablation of miR-200b/a/429 in adipocytes of mice fed a high-fat diet increases adiposity, body weight, and insulin resistance.AtherosclerosisThere is evidence for a role of miR-200 in atherosclerosis. Our preliminary results show that circulating miR-200c is elevated in children with familial hypercholesterolemia. Furthermore, there is a positive correlation between circulating miR-200c and miR-33a and miR-33b, 2 miRNAs upregulated in familial hypercholesterolemia.10Moreover, miR-200b single nucleotide polymorphism T>C may lead to atherosclerosis and stroke, possibly because of failure to downmodulate the regulatory subunit of protein kinase A, which is involved in the suppression of platelet activation and aggregation.IschemiaMiR-200 members increase in the ischemic skeletal muscle1 and also in the brain, in response to ischemia and ischemia/reperfusion.11 To date, the effect of prolonged ischemia, preconditioning, and ischemia/reperfusion injury have not been evaluated in the heart and in other tissues and organs other than the skeletal muscle and brain.Vascular DysfunctionSome miR-200c targets are highly relevant to vascular function. MiR-200c targets directly the 3′untranslated region of SIRT1, endothelial nitric oxide synthase, and forkhead box O1 and disrupts the regulatory loop among these factors.7 Downmodulation of SIRT1 leads to increased acetylation of its targets, forkhead box O1, and p53; acetylated p53 exhibits enhanced transcriptional activity, induces apoptosis, and increases ROS production; acetylation inhibits forkhead box O1 transcriptional activity and via this mechanism decreases SIRT1, catalase, and manganese superoxide dismutase. Therefore, the final results are as follows: (1) an increase in ROS production, corroborated also by p66Shc phosphorylation in Serine 36 and by the downregulation of the H2O2 scavenger peroxiredoxin 2; (2) a decrease in NO availability. These results were validated in human skin fibroblasts from old donors, femoral arteries from old mice, and a mouse model of hindlimb ischemia.Angiogenesis ImpairmentMiR-200 inhibits angiogenesis via different mechanisms. MiR-200b directly targets ETS1 (ETS proto-oncogene 1), a transcription factor with a proangiogenic action linked to its ability to enhance vascular endothelial growth factor (VEGF)-A, VEGF receptor 1 (VEGFR1), and VEGFR2 expression, as well as the expression of hepatocyte growth factor, urokinase, and some matrix metalloproteins. In diabetic mice, miR-200b inhibits cutaneous wound angiogenesis by targeting VEGF, VEGFR1, and VEGFR2, as well as GATA2 and ETS1, transcription factors required for VEGFR2 transcription.12 Moreover, miR-200c targets endothelial nitric oxide synthase7 and VEGFR2.FibrosisThe effect of miR-200 on fibrosis has been examined in the kidney, in the lung, and in cancer.Human and animal studies have shown that enhanced miR-200 expression has an antifibrotic effect and that miR-200 is downregulated in renal and pulmonary fibrosis; furthermore, ZEB1 induces lysyl oxidase-like 2, an enzyme that cross-links and stabilizes collagen in tumor tissue. In contrast, miR-200 can be profibrotic in mesangial cells. Notably, there is a reciprocal link between miR-200 and transforming growth factor-β, a profibrotic cytokine; miR-200 is downregulated by transforming growth factor-β1 and miR-141 targets transforming growth factor-β2. The role of miR-200 on cardiac fibrosis remains to be determined.ArrhythmiasIn vitro experiments have shown that miR-200 targets and downmodulates the expression of sodium voltage-gated channel α-subunit 5 (SCN5A/Nav1.5) in mouse HL-1 myocardial cells, suggesting a role for these miRNAs in cardiac arrhythmias.13Stem Cell DifferentiationFew studies have examined the role of miR-200 in stem cell differentiation toward the vascular and myocardial lineages.In mouse embryonic stem cells miR-200 increase in NO-dependent differentiation toward mesendoderm and cardiovascular lineage.14 Moreover, miR-200c and miR-141 increase in human embryonic stem cells differentiating toward the endothelial lineage. Finally, miR-200c* modulates hanging drop–induced cardiac differentiation of ES cells. The role of miR-200 in stem and progenitor cell differentiation and cardiovascular repair is still unknown.miR-200 Potential Role in Cardiovascular DiseasesBoth acute and chronic conditions are expected to modulate miR-200 expression in the cardiovascular system. For instance, cardiac ischemia/reperfusion should markedly and transiently enhance miR-200 expression. However, it is unknown whether this occurs and, eventually, has an effect on cell death, regeneration, fibrosis, contraction, and arrhythmias. In contrast, there is evidence of a link between miR-200 and diabetes mellitus, obesity, and atherosclerosis; furthermore, miR-200 exhibits an age-dependent increase that may parallel the prevalence and severity of diabetes mellitus and atherosclerosis in the aging population. Is the increase in miR-200 relevant in age-dependent insulin resistance, vascular dysfunction, and impaired angiogenesis? Because of its effect on the epigenetic machinery, may miR-200 be responsible for the chromatin opening and consequent expression of aging- and cardiovascular disease–related genes? Is it possible that pharmacological epigenetic repressors of miR-200 be effective in attenuating noxious miR-200 effects on the cardiovascular system? Interventions aimed at decreasing miR-200 expression, for example, anti-miRNAs, may enhance epithelial–mesenchymal transition and carry an oncogenic risk. In fact, although most studies suggest a detrimental role of miR-200 in the cardiovascular system, it is possible that the age-dependent increase in miR-200 may have a protective role and inhibit cancer development in the elderly. It will be important to establish whether miR-200 downmodulation is tumorigenic, and eventually, which tissues are more likely to form tumors. Since the heart and blood vessels, are less prone to cancer development than other tissues/organs, one way to limit the oncogenic risk of miR-200 downmodulation would be to avoid systemic exposure to the anti-miRNAs.In conclusion, the consequences of miR-200 increase will depend on different factors: which miR-200 members are modulated, the magnitude and time course of the change, the cell type in which the change/s occur, the release of miRNA in the extracellular space, and the presence of other interacting factors, including other ROS-modulated miRNAs. It will be a complex picture to decipher. Nevertheless, miR-200 may account for some features of common diseases and also represents a potential novel therapeutic target.Sources of FundingThis study was supported by Ministero della Salute: GR-2010-2309531 to A. Magenta; RF-2010-2318330 and RC-2016 to M.C. Capogrossi. AIRC-IG2011-ID11793 to M.C. Capogrossi.DisclosuresNone.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.The online-only Data Supplement is available with this article at http://circres.ahajournals.org/lookup/suppl/doi:10.1161/CIRCRESAHA.116.310274/-/DC1.Correspondence to Maurizio C. Capogrossi, MD, Istituto Dermopatico dell'Immacolata-IRCCS, FLMM, Laboratorio di Patologia Vascolare, Via dei Monti di Creta 104, Rome 00167, Italy. E-mail [email protected]References1. Magenta A, Cencioni C, Fasanaro P, Zaccagnini G, Greco S, Sarra-Ferraris G, Antonini A, Martelli F, Capogrossi MC. miR-200c is upregulated by oxidative stress and induces endothelial cell apoptosis and senescence via ZEB1 inhibition.Cell Death Differ. 2011; 18:1628–1639. doi: 10.1038/cdd.2011.42.CrossrefMedlineGoogle Scholar2. Iliopoulos D, Lindahl-Allen M, Polytarchou C, Hirsch HA, Tsichlis PN, Struhl K. Loss of miR-200 inhibition of Suz12 leads to polycomb-mediated repression required for the formation and maintenance of cancer stem cells.Mol Cell. 2010; 39:761–772. doi: 10.1016/j.molcel.2010.08.013.CrossrefMedlineGoogle Scholar3. Wellner U, Schubert J, Burk UC, Schmalhofer O, Zhu F, Sonntag A, Waldvogel B, Vannier C, Darling D, zur Hausen A, Brunton VG, Morton J, Sansom O, Schüler J, Stemmler MP, Herzberger C, Hopt U, Keck T, Brabletz S, Brabletz T. The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs.Nat Cell Biol. 2009; 11:1487–95. doi: 10.1038/ncb1998.CrossrefMedlineGoogle Scholar4. Eades G, Yao Y, Yang M, Zhang Y, Chumsri S, Zhou Q. miR-200a regulates SIRT1 expression and epithelial to mesenchymal transition (EMT)-like transformation in mammary epithelial cells.J Biol Chem. 2011; 286:25992–6002. doi: 10.1074/jbc.M111.229401.CrossrefMedlineGoogle Scholar5. Illi B, Ciarapica R, Capogrossi MC. Chromatin methylation and cardiovascular aging.J Mol Cell Cardiol. 2015; 83:21–31. doi: 10.1016/j.yjmcc.2015.02.011.CrossrefMedlineGoogle Scholar6. Capri M, Olivieri F, Lanzarini C, Remondini D, Borrelli V, Lazzarini R, Graciotti L, Albertini MC, Bellavista E, Santoro A, Biondi F, Tagliafico E, Tenedini E, Morsiani C, Pizza G, Vasuri F, D'Errico-Grigioni A, Dazzi A, Pellegrini S, Magenta A, D'Agostino M, Capogrossi MC, Cescon M, Rippo MR, Procopio AD, Fransceschi C, Grazi GL. Identification of miRs -31, -141, -200c and GLT1 as human liver aging markers sensitive to donor-recipient age mismatch in transplants.Aging Cell. 2016; 16:262–272. doi: 10.1111/acel.12549.CrossrefMedlineGoogle Scholar7. Carlomosti F, D'Agostino M, Beji S, Torcinaro A, Rizzi R, Zaccagnini G, Maimone B, Di Stefano V, De Santa F, Cordisco S, Antonini A, Ciarapica R, Dellambra E, Martelli F, Avitabile D, Capogrossi MC, Magenta A. Oxidative stress-induced miR-200c disrupts the regulatory loop among SIRT1, FOXO1 and eNOS [published online ahead of print January 19, 2017].Antioxid Redox Signal. doi: 10.1089/ars.2016.6643.Google Scholar8. Belgardt BF, Ahmed K, Spranger M, Latreille M, Denzler R, Kondratiuk N, von Meyenn F, Villena FN, Herrmanns K, Bosco D, Kerr-Conte J, Pattou F, Rülicke T, Stoffel M. The microRNA-200 family regulates pancreatic beta cell survival in type 2 diabetes.Nat Med. 2015; 21:619–627. doi: 10.1038/nm.3862.CrossrefMedlineGoogle Scholar9. Hyun S, Lee JH, Jin H, Nam J, Namkoong B, Lee G, Chung J, Kim VN. Conserved MicroRNA miR-8/miR-200 and its target USH/FOG2 control growth by regulating PI3K.Cell. 2009; 139:1096–1108. doi: 10.1016/j.cell.2009.11.020.CrossrefMedlineGoogle Scholar10. Martino F, Carlomosti F, Avitabile D, Persico L, Picozza M, Barillà F, Arca M, Montali A, Martino E, Zanoni C, Parrotto S, Magenta A. Circulating miR-33a and miR-33b are up-regulated in familial hypercholesterolaemia in paediatric age.Clin Sci (Lond). 2015; 129:963–972. doi: 10.1042/CS20150235.CrossrefMedlineGoogle Scholar11. Lee ST, Chu K, Jung KH, Yoon HJ, Jeon D, Kang KM, Park KH, Bae EK, Kim M, Lee SK, Roh JK. MicroRNAs induced during ischemic preconditioning.Stroke. 2010; 41:1646–1651. doi: 10.1161/STROKEAHA.110.579649.LinkGoogle Scholar12. Chan YC, Roy S, Khanna S, Sen CK. Downregulation of endothelial microRNA-200b supports cutaneous wound angiogenesis by desilencing GATA binding protein 2 and vascular endothelial growth factor receptor 2.Arterioscler Thromb Vasc Biol. 2012; 32:1372–1382. doi: 10.1161/ATVBAHA.112.248583.LinkGoogle Scholar13. Daimi H, Lozano-Velasco E, Haj Khelil A, Chibani JB, Barana A, Amorós I, González de la Fuente M, Caballero R, Aranega A, Franco D. Regulation of SCN5A by microRNAs: miR-219 modulates SCN5A transcript expression and the effects of flecainide intoxication in mice.Heart Rhythm. 2015; 12:1333–1342. doi: 10.1016/j.hrthm.2015.02.018.CrossrefMedlineGoogle Scholar14. Rosati J, Spallotta F, Nanni S, Grasselli A, Antonini A, Vincenti S, Presutti C, Colussi C, D'Angelo C, Biroccio A, Farsetti A, Capogrossi MC, Illi B, Gaetano C. Smad-interacting protein-1 and microRNA 200 family define a nitric oxide-dependent molecular circuitry involved in embryonic stem cell mesendoderm differentiation.Arterioscler Thromb Vasc Biol. 2011; 31:898–907. doi: 10.1161/ATVBAHA.110.214478.LinkGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Du M, Espinosa-Diez C, Liu M, Ahmed I, Mahan S, Wei J, Handen A, Chan S and Gomez D (2022) miRNA/mRNA co-profiling identifies the miR-200 family as a central regulator of SMC quiescence, iScience, 10.1016/j.isci.2022.104169, 25:5, (104169), Online publication date: 1-May-2022. Song Y, Tran M, Wang L, Shin D and Wu J (2021) MiR-200c-3p targets SESN1 and represses the IL-6/AKT loop to prevent cholangiocyte activation and cholestatic liver fibrosis, Laboratory Investigation, 10.1038/s41374-021-00710-6, 102:5, (485-493), Online publication date: 1-May-2022. Abdallah H, Hassan R, Fareed A, Abdelgawad M, Mostafa S and Mohammed E (2022) Identification of a circulating microRNAs biomarker panel for non-invasive diagnosis of coronary artery disease: case–control study, BMC Cardiovascular Disorders, 10.1186/s12872-022-02711-9, 22:1, Online publication date: 1-Dec-2022. Prasad V, Makkaoui N, Rajan R, Patel A, Mainali B, Bagchi P, Kumar R, Rogers J, Diamond J and Maxwell J (2022) Loss of cardiac myosin light chain kinase contributes to contractile dysfunction in right ventricular pressure overload, Physiological Reports, 10.14814/phy2.15238, 10:7, Online publication date: 1-Apr-2022. Stachon T, Nastaranpour M, Seitz B, Meese E, Latta L, Taneri S, Ardjomand N, Szentmáry N and Ludwig N (2022) Altered Regulation of mRNA and miRNA Expression in Epithelial and Stromal Tissue of Keratoconus Corneas, Investigative Opthalmology & Visual Science, 10.1167/iovs.63.8.7, 63:8, (7), Online publication date: 11-Jul-2022. Wang D, Xiao Y, Li W, Feng X, Yi G, Chen Z, Wu J and Chen W (2022) Association of noise exposure, plasma microRNAs with arterial stiffness among Chinese workers, Environmental Pollution, 10.1016/j.envpol.2022.120002, 311, (120002), Online publication date: 1-Oct-2022. Nachtigall P, Bovolenta L, Patton J, Fromm B, Lemke N and Pinhal D (2021) A comparative analysis of heart microRNAs in vertebrates brings novel insights into the evolution of genetic regulatory networks, BMC Genomics, 10.1186/s12864-021-07441-4, 22:1, Online publication date: 1-Dec-2021. Zia A, Sahebdel F, Farkhondeh T, Ashrafizadeh M, Zarrabi A, Hushmandi K and Samarghandian S (2021) A review study on the modulation of SIRT1 expression by miRNAs in aging and age-associated diseases, International Journal of Biological Macromolecules, 10.1016/j.ijbiomac.2021.08.013, 188, (52-61), Online publication date: 1-Oct-2021. Raza S, Abdelnour S, Dhshan A, Hassanin A, Noreldin A, Albadrani G, Abdel-Daim M, Cheng G and Zan L (2021) Potential role of specific microRNAs in the regulation of thermal stress response in livestock, Journal of Thermal Biology, 10.1016/j.jtherbio.2021.102859, 96, (102859), Online publication date: 1-Feb-2021. Li H, Zou J, Yu X, Ou X and Tang C (2020) Zinc finger E‐box binding homeobox 1 and atherosclerosis: New insights and therapeutic potential, Journal of Cellular Physiology, 10.1002/jcp.30177, 236:6, (4216-4230), Online publication date: 1-Jun-2021. Florio M, Magenta A, Beji S, Lakatta E and Capogrossi M (2020) Aging, MicroRNAs, and Heart Failure, Current Problems in Cardiology, 10.1016/j.cpcardiol.2018.12.003, 45:12, (100406), Online publication date: 1-Dec-2020. Jiang Y, Yang Y, Zhang C, Huang W, Wu L, Wang J, Su M, Sun D and Gao Y (2020) Upregulation of miR-200c-3p induced by NaF promotes endothelial apoptosis by activating Fas pathway, Environmental Pollution, 10.1016/j.envpol.2020.115089, 266, (115089), Online publication date: 1-Nov-2020. Nabih H (2020) Crosstalk between NRF2 and Dicer through metastasis regulating MicroRNAs; mir-34a, mir-200 family and mir-103/107 family, Archives of Biochemistry and Biophysics, 10.1016/j.abb.2020.108326, 686, (108326), Online publication date: 1-Jun-2020. Banerjee A, Bhattacharya R and Mal C (2020) HMG2D: A tool to identify miRNAs/drugs/genes associated with diseases like cancers, Meta Gene, 10.1016/j.mgene.2020.100699, 24, (100699), Online publication date: 1-Jun-2020. Xue Y, Fan X, Yang R, Jiao Y and Li Y (2020) miR-29b-3p inhibits post-infarct cardiac fibrosis by targeting FOS, Bioscience Reports, 10.1042/BSR20201227, 40:9, Online publication date: 30-Sep-2020. Salama A, Duque M, Wang L, Shahzad K, Olivera M and Loor J (2019) Enhanced supply of methionine or arginine alters mechanistic target of rapamycin signaling proteins, messenger RNA, and microRNA abundance in heat-stressed bovine mammary epithelial cells in vitro, Journal of Dairy Science, 10.3168/jds.2018-15219, 102:3, (2469-2480), Online publication date: 1-Mar-2019. Li W, Zhang D, Wang W, Wu Y, Mohammadnejad A, Lund J, Baumbach J, Christiansen L and Tan Q (2019) DNA methylome profiling in identical twin pairs discordant for body mass index, International Journal of Obesity, 10.1038/s41366-019-0382-4, 43:12, (2491-2499), Online publication date: 1-Dec-2019. Yuan T, Yang T, Chen H, Fu D, Hu Y, Wang J, Yuan Q, Yu H, Xu W and Xie X (2019) New insights into oxidative stress and inflammation during diabetes mellitus-accelerated atherosclerosis, Redox Biology, 10.1016/j.redox.2018.09.025, 20, (247-260), Online publication date: 1-Jan-2019. Wu H, Wu J and Ni Z (2019) RETRACTED ARTICLE: Overexpression of microRNA-202-3p protects against myocardial ischemia-reperfusion injury through activation of TGF-β1/Smads signaling pathway by targeting TRPM6, Cell Cycle, 10.1080/15384101.2019.1580494, 18:5, (621-637), Online publication date: 4-Mar-2019. Yang X, Chen G and Chen Z (2019) MicroRNA-200a-3p Is a Positive Regulator in Cardiac Hypertrophy Through Directly Targeting WDR1 as Well as Modulating PTEN/PI3K/AKT/CREB/WDR1 Signaling, Journal of Cardiovascular Pharmacology, 10.1097/FJC.0000000000000732, 74:5, (453-461), Online publication date: 1-Nov-2019. Abu-Halima M, Kahraman M, Henn D, Rädle-Hurst T, Keller A, Abdul-Khaliq H and Meese E (2018) Deregulated microRNA and mRNA expression profiles in the peripheral blood of patients with Marfan syndrome, Journal of Translational Medicine, 10.1186/s12967-018-1429-3, 16:1, Online publication date: 1-Dec-2018. Patel N, Moss L, Lee J, Tajiri N, Acosta S, Hudson C, Parag S, Cooper D, Borlongan C and Bickford P (2018) Long noncoding RNA MALAT1 in exosomes drives regenerative function and modulates inflammation-linked networks following traumatic brain injury, Journal of Neuroinflammation, 10.1186/s12974-018-1240-3, 15:1, Online publication date: 1-Dec-2018. Thiriet M (2018) Cardiovascular Risk Factors and Markers Vasculopathies, 10.1007/978-3-319-89315-0_2, (91-198), . D'Agostino M, Martino F, Sileno S, Barillà F, Beji S, Marchetti L, Gangi F, Persico L, Picozza M, Montali A, Martino E, Zanoni C, Avitabile D, Parrotto S, Capogrossi M and Magenta A (2017) Circulating miR-200c is up-regulated in paediatric patients with familial hypercholesterolaemia and correlates with miR-33a/b levels: implication of a ZEB1-dependent mechanism , Clinical Science, 10.1042/CS20171121, 131:18, (2397-2408), Online publication date: 15-Sep-2017. Sidorkiewicz I, Jóźwik M, Niemira M and Krętowski A (2020) Insulin Resistance and Endometrial Cancer: Emerging Role for microRNA, Cancers, 10.3390/cancers12092559, 12:9, (2559) Qadir M, Klein D, Álvarez-Cubela S, Domínguez-Bendala J and Pastori R (2019) The Role of MicroRNAs in Diabetes-Related Oxidative Stress, International Journal of Molecular Sciences, 10.3390/ijms20215423, 20:21, (5423) Perdoncin M, Konrad A, Wyner J, Lohana S, Pillai S, Pereira D, Lakhani H and Sodhi K (2021) A Review of miRNAs as Biomarkers and Effect of Dietary Modulation in Obesity Associated Cognitive Decline and Neurodegenerative Disorders, Frontiers in Molecular Neuroscience, 10.3389/fnmol.2021.756499, 14 Włodarski A, Strycharz J, Wróblewski A, Kasznicki J, Drzewoski J and Śliwińska A (2020) The Role of microRNAs in Metabolic Syndrome-Related Oxidative Stress, International Journal of Molecular Sciences, 10.3390/ijms21186902, 21:18, (6902) Riehle C, Sieweke J, Bakshi S, Ha C, Junker Udesen N, Møller-Helgestad O, Froese N, Berg Ravn H, Bähre H, Geffers R, Seifert R, Møller J, Wende A, Bauersachs J and Schäfer A (2022) miRNA-200b—A Potential Biomarker Identified in a Porcine Model of Cardiogenic Shock and Mechanical Unloading, Frontiers in Cardiovascular Medicine, 10.3389/fcvm.2022.881067, 9 Dehaini H, Awada H, El-Yazbi A, Zouein F, Issa K, Eid A, Ibrahim M, Badran A, Baydoun E, Pintus G and Eid A (2019) MicroRNAs as Potential Pharmaco-targets in Ischemia-Reperfusion Injury Compounded by Diabetes, Cells, 10.3390/cells8020152, 8:2, (152) Nikolajevic J, Ariaee N, Liew A, Abbasnia S, Fazeli B and Sabovic M (2022) The Role of MicroRNAs in Endothelial Cell Senescence, Cells, 10.3390/cells11071185, 11:7, (1185) Zhang L, Men X, Yu S, Guo H, Luo Y, Chen H and Mi S (2022) Ozone protects cardiomyocytes from myocardial ischemia–reperfusion injury through miR-200c/FOXO3 axis, Journal of Receptors and Signal Transduction, 10.1080/10799893.2022.2060259, (1-9) Scioli M, Storti G, D'Amico F, Rodríguez Guzmán R, Centofanti F, Doldo E, Céspedes Miranda E and Orlandi A (2020) Oxidative Stress and New Pathogenetic Mechanisms in Endothelial Dysfunction: Potential Diagnostic Biomarkers and Therapeutic Targets, Journal of Clinical Medicine, 10.3390/jcm9061995, 9:6, (1995) Zhao X, Ling F, Zhang G, Yu N, Yang J and Xin X (2022) The Correlation Between MicroRNAs and Diabetic Retinopathy, Frontiers in Immunology, 10.3389/fimmu.2022.941982, 13 April 28, 2017Vol 120, Issue 9 Advertisement Article InformationMetrics © 2017 American Heart Association, Inc.https://doi.org/10.1161/CIRCRESAHA.116.310274PMID: 28450364 Originally publishedApril 28, 2017 Keywordscardiovascular diseasesmicroRNAsinsulin resistanceoxidative stressagingPDF download Advertisement SubjectsEndothelium/Vascular Type/Nitric OxideInflammationMetabolic SyndromeOxidant StressVascular Disease
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