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Increased expression of miR-33a in monocytes from Mexican hypertensive patients in elevated carotid intima-media thickness

Journal of Human Hypertension volume 32, pages 681–690 (2018)Cite this article

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A Comment to this article was published on 19 September 2018

Abstract

miR-33a has been described as a key regulator in the initiation and progression of atherosclerosis. However, its role in arterial hypertension (HTA) has not been elucidated. Therefore, the aim of this study was to determine the association between the expression of miR-33a (5p and 3p) and the carotid intima-media thickness (cIMT) in samples of monocytes and serum from hypertensive patients. The miR-33a-5p and miR-33a-3p expression in monocytes and serum from Mexican hypertensive patients were examined by RT-PCR. This study involved 84 subjects (42 normotensive subjects and 42 patients with essential hypertension). Our study revealed that miR-33a-5p expression was significantly upregulated in the monocytes of hypertensive patients compared with the control group (p = 0.001), while miR-33a-3p was significantly downregulated (p = 0.013). miR-33a-5p upregulation [OR: 5.53, 95% CI: 2.01–15.20; p = 0.001], as well as miR-33a-3p downregulation [OR: 3.32, 95% CI: 1.45–7.60; p = 0.004] in monocytes, was associated with an increased risk of developing hypertension. In addition, miR-33a-5p upregulation in hypertensive patients was associated with an increased risk of presenting cIMT [OR: 5.99, 95% CI: 1.10–32.85; p = 0.039]. Moreover, we found no significant differences in the expression of both strands of miR-33a in serum of our patients. Our results showed an upregulation of miR-33a-5p and downregulation of miR-33a-3p in monocytes, these data are associated with cIMT, which could be a risk factor for the development of hypertension. In addition, upregulation of miR-33a-5p in monocytes from Mexican hypertensive patients could be involved in the development of atherosclerosis.

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References

  1. World Health Organization. A global brief on hypertension: silent killer, global public health crisis. Geneva: WHO; 2013.

  2. Lahera V. Hipertensión y aterosclerosis: relación entre el perfil circadiano de la presión arterial y el grosor íntima-media carotídeo. Clín Invest Arterioscler. 2003;21:23–4.

    Article  Google Scholar 

  3. Mateo I, Morillas P, Quiles J, Castillo J, Andrade H, Roldán J, et al. What measure of carotid wall thickening is the best atherosclerotic loading score in the hypertensive patient: maximum or mean value? Rev Esp Cardiol. 2011;64:417–20.

    Article  Google Scholar 

  4. Llorente-Cortés V, Royo T, Otero-Viñas M, Berrozpe M, Badimon L. Sterol regulatory element binding proteins downregulate LDL receptor-related protein (LRP1) expression and LRP1-mediated aggregated LDL uptake by human macrophages. Cardiovasc Res. 2007;74:526–36.

    Article  Google Scholar 

  5. Robinet P, Védie B, Chironi G, Gariépy J, Simon A, Moatti N, et al. Characterization of polymorphic structure of SREBP-2 gene: role in atherosclerosis. Atherosclerosis. 2003;168:381–7.

    Article  CAS  Google Scholar 

  6. Costales P, Castellano J, Revuelta-López E, Cal R, Aledo R, Llampayas O, et al. Lipopolysaccharide downregulates CD91/low-density lipoprotein receptor-related protein 1 expression through SREBP1 overexpression in human macrophages. Atherosclerosis. 2012;227:79–88.

    Article  Google Scholar 

  7. Ono K, Horie T, Nishino T, Baba O, Kuwabara Y, Kimura T. MicroRNAs and high-density lipoprotein cholesterol metabolism. Int Heart J. 2015;56:365–71.

    Article  CAS  Google Scholar 

  8. Ono K. Functions of microRNA-33a/b and microRNA therapeutics. J Cardiol. 2016;67:28–33.

    Article  Google Scholar 

  9. Brown MS, Ye J, Goldstein JL. Medicine. HDL miR-ed down by SREBP introns. Science. 2010;328:1495–6.

    Article  CAS  Google Scholar 

  10. Chen WJ, Zhang M, Zhao GJ, Fu Y, Zhang DW, Zhu HB, Tang CK. MicroRNA-33 in atherosclerosis etiology and pathophysiology. Atherosclerosis. 2013;227:201–8.

    Article  CAS  Google Scholar 

  11. Novák J, Olejníčková V, Tkáčová N, Santulli G. Mechanistic role of microRNAs in coupling lipid metabolism and atherosclerosis. Adv Exp Med Biol. 2015;887:79–100.

    Article  Google Scholar 

  12. Horie T, Baba O, Kuwabara Y, Yokode M, Kita T, Kimura T, et al. MicroRNAs and lipoprotein metabolism. J Atheroscler Thromb. 2013;21:17–22.

    PubMed  Google Scholar 

  13. Friedewald WT, Levi RI, Fredrickson DS. Estimation of concentration of low density lipoproteins cholesterol in plasma without use of the preparative ultracentrifuge. Clin Chem. 1972;18:499–502.

    CAS  PubMed  Google Scholar 

  14. De Long DA, De Long ER, Weed PD. The comparation of methods for the estimation of plasma low and very low density lipoproteins cholesterol. J Am Med Assoc. 1986;286:2372–7.

    Google Scholar 

  15. Stein JH, Korcarz CE, Hurst RT, Lonn E, Kendall CB, Mohler ER, et al. Use of carotid ultrasound to identify subclinical vascular disease and evaluate cardiovascular disease risk: a consensus statement from the American Society of Echocardiography Carotid Intima-Media Thickness Task Force Endorsed by the Society for Vascular Medicine. J Am Soc Echocardiogr. 2008;21:93–111.

    Article  Google Scholar 

  16. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCq method. Methods. 2001;25:402–8.

    Article  CAS  Google Scholar 

  17. Dong J, Liang YZ, Zhang J, Wu LJ, Wang S, Hua Q, Yan YX. Potential role of lipometabolism-related microRNAs in peripheral blood mononuclear cells as biomarkers for coronary artery disease. J Atheroscler Thromb. 2017;24:430–41.

    Article  CAS  Google Scholar 

  18. Rayner KJ, Sheedy FJ, Esau CC, Hussain FN, Temel RE, Parathath S, et al. Antagonism of miR-33 in mice promotes reverse cholesterol transport and regression of atherosclerosis. J Clin Invest. 2011;121:2921–31.

    Article  CAS  Google Scholar 

  19. Marquart TJ, Allen RM, Ory DS. Baldan A. Mir-33 links srebp-2 induction to repression of sterol transporters. Proc Natl Acad Sci USA. 2010;107:12228–32.

    Article  CAS  Google Scholar 

  20. Rayner KJ, Fernandez-Hernando C, Moore KJ. MicroRNAs regulating lipid metabolism in atherogenesis. Thromb Haemost. 2012;107:642e7.

    Article  Google Scholar 

  21. Rayner KJ, Esau CC, Hussain FN, McDaniel AL, Marshal SM, van Gils JM, et al. Inhibition of miR-33a/b in non-human primates raises plasma HDL and lowers VLDL triglycerides. Nature. 2011;478:404e7.

    Article  Google Scholar 

  22. Choo KB, Soon YL, Nguyen PN, Hiew MS, Huang CJ. MicroRNA-5p and -3p co-expression and cross-targeting in colon cancer cells. J Biomed Sci. 2014;21:95.

    Article  Google Scholar 

  23. Jagadeeswaran G, Zheng Y, Sumathipala N, Jiang H, Arrese EL, Soulages JL, et al. Deep sequencing of small RNA libraries reveals dynamic regulation of conserved and novel microRNAs and microRNA-stars during silkworm development. BMC Genomics. 2010;11:52.

    Article  Google Scholar 

  24. Huang C, Nguyen P, Choo K, Sugii S, Wee K, Cheong S, et al. Frequent co-expression of miRNA-5p and -3p species and cross-targeting in induced pluripotent stem cells. Int J Med Sci. 2010;11:824–33.

    Article  Google Scholar 

  25. Fornari F, Milazzo M, Chieco P, Negrini M, Calin GA, Grazi GL, et al. MiR-199a-3p regulates mTOR and c-Met to influence the doxorubicin sensitivity of human hepatocarcinoma cells. Cancer Res. 2010;70:5184–93.

    Article  CAS  Google Scholar 

  26. Packer AN, Xing Y, Harper SQ, Jones L, Davidson BL. The bifunctional microRNA miR-9/miR-9* regulates REST and CoREST and is downregulated in Huntington’s disease. J Neurosci. 2008;28:14341–6.

    Article  CAS  Google Scholar 

  27. Schwarz PD, Hutvagner G, Du T, Xu ZS, Aroni N, Zamore PD. Asymmetry in the assembly of the RNAi enzyme complex. Cell. 2003;115:199–208.

    Article  CAS  Google Scholar 

  28. Khvorova A, Reynolds A, Jayasena SD. Functional siRNAs and miRNAs exhibit strand bias. Cell. 2003;115:209–16.

    Article  CAS  Google Scholar 

  29. Ro S, Park C, Young D, Sanders KM, Yan W. Tissue-dependent paired expression of miRNAs. Nucleic Acids Res. 2007;35:5944–53.

    Article  CAS  Google Scholar 

  30. Tsai KW, Leung CM, Lo YH, Chen TW, Chan WC, Yu SY, et al. Arm selection preference of microRNA-193a varies in breast cancer. Sci Rep. 2016;6:28176.

    Article  CAS  Google Scholar 

  31. Weber JA, Baxter DH, Zhang S, Huang DY, Huang KH, Lee MJ, et al. The microRNA spectrum in 12 body fluids. Clin Chem. 2010;56:1733–41.

    Article  CAS  Google Scholar 

  32. De Gonzalo-Calvo D, Iglesias-Gutiérrez E, Llorente-Cortés V. Epigenetic biomarkers and cardiovascular disease: circulating microRNAs. Rev Esp Cardiol. 2017;70:763–9.

    Article  Google Scholar 

  33. Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA. 2008;105:10513–8.

    Article  CAS  Google Scholar 

  34. Xiao Y, Christou H, Liu L, Visner G, Mitsialis A, Kourembanas S, Liu H. Endothelial indoleamine 2,3-dioxygenase protects against development of pulmonary hypertension. Am J Respir Crit Care Med. 2013;188:482–91.

    Article  CAS  Google Scholar 

  35. Nossent AY, et al. The 14q32 microRNA-487b targets the antiapoptotic insulin receptor substrate 1 in hypertension-induced remodeling of the aorta. Ann Surg. 2013;258:743–51.

    Article  Google Scholar 

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Acknowledgements

We thank the participants of this study.

Funding

Funding for this study was provided by Consejo Nacional de Ciencia y Tecnologia, Project Number 273022.

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Author notes

  1. These authors contributed equally: Torres-Paz Yazmín Estela, Huesca-Gómez Claudia

Authors and Affiliations

  1. Department of Physiology, Instituto Nacional de Cardiología “Ignacio Chávez”, México City, Mexico

    Yazmín Estela Torres-Paz, Claudia Huesca-Gómez, Giovanny Fuentevilla-Álvarez & Ricardo Gamboa

  2. Department of Immunology, Instituto Nacional de Cardiología “Ignacio Chávez”, México City, Mexico

    Fausto Sánchez-Muñoz & Ma.Elena Soto

  3. Department of Endocrinology, Instituto Nacional de Cardiología “Ignacio Chávez”, México City, Mexico

    Rocío Martínez-Alvarado & Margarita Torres-Tamayo

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  1. Yazmín Estela Torres-Paz
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Correspondence to Ricardo Gamboa.

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Torres-Paz, Y.E., Huesca-Gómez, C., Sánchez-Muñoz, F. et al. Increased expression of miR-33a in monocytes from Mexican hypertensive patients in elevated carotid intima-media thickness. J Hum Hypertens 32, 681–690 (2018). https://doi.org/10.1038/s41371-018-0102-x

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