Association between the transporters ABCA1/G1 and the expression of miR-33a/144 and the carotid intima media thickness in patients with arterial hypertension
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ATP-binding cassette membrane transporters (ABC), functions as an outflow facilitator of phospholipids and cellular cholesterol, playing an important role in the development of atherosclerosis and arterial hypertension. ABC’s transporters could post-transcriptionally regulated by miRs. Evaluate the association in the transporters ABCA1 and ABCG1 with the expression of miR-33a and miR-144 and the carotid intima media thickness (cIMT) in patients with essential arterial hypertension. The miR-33a-5p, miR-144-3p and mRNA ABCA1 and ABCG1 expression in monocytes from Mexican hypertensive patients were examined by RT-PCR. The miR-33a and miR-144 expression in monocytes and mRNA ABCA1 and ABCG1 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 expression (p = 0.001) and miR-144 (p = 0.985) were up-regulated, meanwhile, ABCA1 and ABCG1 transporters were down-regulated (p = 0.007 and p = 0.550 respectively) in hypertensive patients compared with the control group. The trend remains for miR33a/ABCA1 in presence of cIMT. Moreover, an inverse correlation was found with the expression levels of ABCA1 and ABCG1 as well as in HDL-C with miR-33a and miR-144. Our results showed an increase in the expression of miR-33a and miR-144 and an inverse correlation in their target ABCA1 and ABCG1; it may be associated with essential arterial hypertension in patients with cIMT and as consequence for atheromatous plaque.
KeywordsmiR-33a miR-144 ABC transporters Arterial hypertension Carotid intima-media thickness
We thank the participants of this study.
Funding for this study was provided by Consejo Nacional de Ciencia y Tecnologia (CONACYT), Project Number 273022. Compliance with ethical standards
Compliance with ethical standards
Conflict of interest
The authors report no conflict of interest.
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (Instituto Nacional de Cardiología, México) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study.
- 2.Ripatti S, Tikkanen E, Orho-Melander M, Havulinna AS, Silander K, Sharma A, Guiducci C, Perola M, Jula A, Sinisalo J, Lokki ML, Nieminen MS, Melander O, Salomaa V, Peltonen L, Kathiresan S (2010) A multilocus genetic risk score for coronary heart disease: case–control and prospective cohort analyses. Lancet 376:1393–1400CrossRefGoogle Scholar
- 7.van Eck M, Bos IS, Kaminski WE, Orsó E, Rothe G, Twisk J, Böttcher A, Van Amersfoort ES, Christiansen-Weber TA, Fung-Leung WP, Van Berkel TJ, Schmitz G (2002) Leukocyte ABCA1 controls susceptibility to atherosclerosis and macrophage recruitment into tissues. Proc Natl Acad Sci USA 99:6298–6303CrossRefGoogle Scholar
- 11.Horie T, Ono K, Horiguchi M, Nishi H, Nakamura T, Nagao K, Kinoshita M, Kuwabara Y, Marusawa H, Iwanaga Y, Hasegawa K, Yokode M, Kimura T, Kita T (2010) MicroRNA-33 encoded by an intron of sterol regulatory element-binding protein 2 (Srebp2) regulates HDL in vivo. Proc Natl Acad Sci USA 107:17321e6CrossRefGoogle Scholar
- 13.Distel E, Barret TJ, Chung K, Gisgis NM, Parathath GS, Essau CC, Murphy AJ, Moore KJ, Fisher ED (2013) MicroRNA-144 regulates hepatic ATP binding cassette transporter A1 and plasma high density lipoprotein after activation of nuclear receptor farnesoid X receptor. Circ Res 112:1602–1612CrossRefGoogle Scholar
- 17.De Long DA, De Long ER, Weed PD (1986) The comparation of methods for the estimation of plasma low and very low density lipoproteins cholesterol. J Am Med Assoc 286:2372–2377Google Scholar
- 18.Stein JH, Korcarz CE, Hurst RT, Lonn E, Kendall CB, Mohler ER, Najjar SS, Rembold CM, Post WS (2008) American Society of Echocardiography Carotid Intima-Media Thickness Task Force. 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. J Am Soc Echocardiogr 21(2):93–111CrossRefGoogle Scholar
- 21.Ramirez CM, Rotllan N, Vlassov AV, Dávalos A, Li M, Goedeke L, Aranda JF, Cirera-Salinas D, Araldi E, Salerno A, Wanschel A, Zavadil J, Castrillo A, Kim J, Suárez Y, Fernández-Hernando C (2013) Control of cholesterol metabolism and plasma HDL levels by miRNA-144. Circ Res 112:1592–1601CrossRefGoogle Scholar
- 22.Rayner KJ, Esau CC, Hussain FN, McDaniel AL, Marshall SM, van Gils JM, Ray TD, Sheedy FJ, Goedeke L, Liu X, Khatsenko OG, Lees CJ, Fernandez-Hernando C, Fisher EA, Temel RE, Moore KJ (2011) Inhibition of miR-33a/b in non-human primates raises plasma HDL and lowers VLDL triglycerides. Nature 478:404e7CrossRefGoogle Scholar
- 24.Raitoharju E, Lyytikainen LP, Levula M, Oksala N, Mennander A, Tarkka M, Klopp N, Illig T, Kähönen M, Karhunen PJ, Laaksonen R, Lehtimäki T (2011) miR-21, miR-210, miR-34a, and miR-146a/b are up-regulated in human atherosclerotic plaques in the Tampere Vascular Study. Atherosclerosis 219:211e7CrossRefGoogle Scholar
- 25.Vega-Badillo J, Gutierrez-Vidal R, Hernandez-Perez HA, Villamil-Ramírez H, León-Mimila P, Sánchez-Muñoz F, Morán-Ramos S, Larrieta-Carrasco E, Fernández-Silva I, Méndez-Sánchez N, Tovar AR, Campos-Pérez F, Villarreal-Molina T, Hernández-Pando R, Aguilar-Salinas CA, Canizales-Quinteros S (2016) Hepatic miR-33a/miR-144 and their target gene ABCA1 are associated with steatohepatitis in morbidly obese subjects. Liver Int 36:1383–1391CrossRefGoogle Scholar