arthyperАртериальная гипертензия"Arterial’naya Gipertenziya" ("Arterial Hypertension")1607-419X2411-8524Antihypertensive League10.18705/1607-419X-2015-21-6-559-566arthyper-338Research ArticleСтатьиArticlesЭпигенетические механизмы в становлении и прогрессировании артериальной гипертензии и ее осложненийEpigenetic mechanisms in hypertension and its complicationsКонрадиА. О.KonradiA. O.

доктор медицинских наук, профессор, руководитель научно-исследовательского отдела артериальной гипертензии, заместитель генерального директора по научной работе ФГБУ «СЗФМИЦ им. В. А. Алмазова» Минздрава России

ул. Аккуратова, д. 2, Санкт-Петербург, Россия, 197341. Тел.: +7(812)702–37–33

MD, PhD, Professor, Deputy General Director on Research, V. A. Almazov Federal North-West Medical Research Centre.

2 Akkuratov street, St Petersburg, 197341 Russia. Phone: +7(812)702–37–33

konradi@almazovcentre.ruФедеральное государственное бюджетное учреждение «Северо-Западный федеральный медицинский исследовательский центр имени В. А. Алмазова» Министерства здравоохранения Российской Федерации, Санкт-Петербург, РоссияРоссияV. A. Almazov Federal North-West Medical Research Centre, St Petersburg, RussiaRussian Federation201502022016216559566Copyright © Конради А.О., 20162016Конради А.О.Konradi A.O.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://htn.almazovcentre.ru/jour/article/view/338

Переворотом в современной медицине стало понимание роли эпигенетической регуляции и возможности передачи из поколения в поколение эпигенетических изменений, которые опосредованы образом жизни и влиянием окружающей среды. Изучение данных механизмов открыло новые перспективы понимания происхождения целого ряда неинфекционных хронических заболеваниях, таких как патология опорно-двигательного аппарата, аутоиммунные заболевания, опухоли, психические расстройства, нейродегенеративные заболевания; впоследствии была показана роль эпигенетических изменений в развитии заболеваний сердечно-сосудистой системы и сахарного диабета. В настоящее время определены основные фундаментальные механизмы эпигенетической регуляции и разрабатываются подходы воздействия на специфические мишени различных эпигенетических компонентов. В представленном обзоре приводятся данные о молекулах, которые уже находятся в стадии клинического изучения и даже одобрены к применению. Исследования в области сердечно-сосудистых заболеваний находятся в стадии активногоизучения и ранних разработок. Эпигенетические механизмы ответственны не только за развитие и дифференцировку сердечно-сосудистых событий, формирование патологий, но и за регенераторный потенциал органов и тканей при их повреждении, за поддержание плюрипотентности и самообновление клеточных популяций. Накопление новых данных поможет сформировать новые концепции развития заболеваний и создать новые инструменты их профилактики и лечения.

The discovery of the epigenetic regulation and the existence of trans-generation transfer of epigenetic changes became a revolutionary finding in modern medicine. These changes are mediated by environmental factors and lifestyle. The understanding of the underlying mechanisms elucidated pathogenesis of some non-infectious chronic pathologies including the diseases of musculoskeletal system, autoimmune diseases, tumors, psychiatric disorders, neurodegenerative disorders. Later, the epigenetic mechanisms were shown to play role in the development of cardiovascular diseases and diabetes mellitus. Nowadays the main, fundamental mechanisms of epigenetic regulation are established, and potential therapeutic approaches targeted at various epigenetic components are under development. This paper reviews different molecules that are studied and are approved. The studies in cardiovascular diseases are ongoing. Epigenetic mechanisms are involved in development of cardiovascular events, and other pathologies, as well as in regeneration of damaged organs and tissues, in the maintenance of pluripotent and regenerative characteristics of cell populations. Collected data will help to understand disease pathogenesis and to develop new prevention and treatment approaches.

эпигенетикапатогенезсердечно-сосудистые заболеванияэкспрессия геновдезоксирибонуклеиновая кислотарибонуклеиновая кислотаобзорepigeneticspathogenesiscardiovascular diseasesgene expressiondeoxyribonucleic acidribonucleic acidreviewReferencesFeinberg AP. Epigenetics at the epicenter of modern medicine. J Am Med Assoc. 2008;299(11):1345–1350.Feinberg AP. Epigenetics at the epicenter of modern medicine. J Am Med Assoc. 2008;299(11):1345–1350.Udali S, Guarini P, Moruzzi S, Choi SW, Friso S. Cardiovascular epigenetics: from DNA methylation to microRNAs. Mol Aspects Med. 2013;34(4):883–901.Udali S, Guarini P, Moruzzi S, Choi SW, Friso S. Cardiovascular epigenetics: from DNA methylation to microRNAs. Mol Aspects Med. 2013;34(4):883–901.Birney E. Chromatin and heritability: how epigenetic studies can complement genetic approaches. Trends Genet. 2011;27 (5):172–176.Birney E. Chromatin and heritability: how epigenetic studies can complement genetic approaches. Trends Genet. 2011;27 (5):172–176.Rasool M, Malik A, Naseer MI, Manan A, Ansari S, Begum I et al. The role of epigenetics in personalized medicine. BMC Medicla Genomics. 2015;8(Suppl 1):S5.Rasool M, Malik A, Naseer MI, Manan A, Ansari S, Begum I et al. The role of epigenetics in personalized medicine. BMC Medicla Genomics. 2015;8(Suppl 1):S5.Creemers, EE, Tijsen AJ, Pinto YM. Circulating microRNAs: novel biomarkers and extracellular communicators in cardiovascular disease? Circ Res. 2012;110(3):483–495.Creemers, EE, Tijsen AJ, Pinto YM. Circulating microRNAs: novel biomarkers and extracellular communicators in cardiovascular disease? Circ Res. 2012;110(3):483–495.Friso S, Choi SW. Gene-nutrient interactions and DNA methylation. J Nutr. 2002;132(8):2382S‑2387S.Friso S, Choi SW. Gene-nutrient interactions and DNA methylation. J Nutr. 2002;132(8):2382S‑2387S.Liang M, Cowley AW Jr, Mattson DL, Kotchen TA, Liu Y. Epigenomics of hypertension. Semin Nephrol. 2013;33 (4):392–9.Liang M, Cowley AW Jr, Mattson DL, Kotchen TA, Liu Y. Epigenomics of hypertension. Semin Nephrol. 2013;33 (4):392–9.Bird AP. CpG-rich islands and the function of DNA methylation. Nature. 1986;321(6067):209–213.Bird AP. CpG-rich islands and the function of DNA methylation. Nature. 1986;321(6067):209–213.Jones PA, Takai D. The role of DNA methylation in mammalian epigenetics. Science 2001;293(5532):1068–1070.Jones PA, Takai D. The role of DNA methylation in mammalian epigenetics. Science 2001;293(5532):1068–1070.Baccarelli A, Rienstra M, Benjamin EJ. Cardiovascular epigenetics: basic concepts and results from animal and human studies. Circ Cardiovasc Genet. 2010;3(6):567–573.Baccarelli A, Rienstra M, Benjamin EJ. Cardiovascular epigenetics: basic concepts and results from animal and human studies. Circ Cardiovasc Genet. 2010;3(6):567–573.Smolarek I, Wyszko E, Barciszewska AM, Nowak S, Gawronska I, Jablecka A et al. Global DNA methylation changes in blood of patients with essential hypertension. Med Sci Monit. 2010;16(3):CR149–CR155.Smolarek I, Wyszko E, Barciszewska AM, Nowak S, Gawronska I, Jablecka A et al. Global DNA methylation changes in blood of patients with essential hypertension. Med Sci Monit. 2010;16(3):CR149–CR155.Terry MB, Delgado-Cruzata L, Vin-Raviv N, Wu HC, Santella RM. DNA methylation in white blood cells: association with risk factors in epidemiologic studies. Epigenetics. 2011;6 (7):828–837.Terry MB, Delgado-Cruzata L, Vin-Raviv N, Wu HC, Santella RM. DNA methylation in white blood cells: association with risk factors in epidemiologic studies. Epigenetics. 2011;6 (7):828–837.Branco MR, Ficz G, Reik W. Uncovering the role of 5‑hydroxymethylcytosine in the epigenome. Nat Rev Genet. 2012;13(1):7–13.Branco MR, Ficz G, Reik W. Uncovering the role of 5‑hydroxymethylcytosine in the epigenome. Nat Rev Genet. 2012;13(1):7–13.Song CX, Yi C, He C. Mapping recently identified nucleotide variants in the genome and transcriptome. Nat Biotechnol. 2012;30(11):1107–1116.Song CX, Yi C, He C. Mapping recently identified nucleotide variants in the genome and transcriptome. Nat Biotechnol. 2012;30(11):1107–1116.Valinluck V, Tsai HH, Rogstad DK, Burdzy A, Bird A, Sowers LC. Oxidative damage to methyl-CpG sequences inhibits the binding of the methyl-CpG binding domain (MBD) of methyl-CpG binding protein 2 (MeCP2). Nucleic Acids Res. 2004;32 (14):4100–4108.Valinluck V, Tsai HH, Rogstad DK, Burdzy A, Bird A, Sowers LC. Oxidative damage to methyl-CpG sequences inhibits the binding of the methyl-CpG binding domain (MBD) of methyl-CpG binding protein 2 (MeCP2). Nucleic Acids Res. 2004;32 (14):4100–4108.Liu Y, Liu P, Yang C, Cowley AW Jr, Liang M. Baseresolution maps of 5‑methylcytosine and 5‑hydroxymethylcytosine in Dahl S rats: effect of salt and genomic sequence. ypertension. 2014;63(4):827–838.Liu Y, Liu P, Yang C, Cowley AW Jr, Liang M. Baseresolution maps of 5‑methylcytosine and 5‑hydroxymethylcytosine in Dahl S rats: effect of salt and genomic sequence. ypertension. 2014;63(4):827–838.Carvajal CA, Gonzalez AA, Romero DG, González A, Mosso LM, Lagos ET et al. Two homozygous mutations in the 11 beta-hydroxysteroid dehydrogenase type 2 gene in a case of apparent mineralocorticoid excess. J Clin Endocrinol Metab. 2003;88(6):2501–2507.Carvajal CA, Gonzalez AA, Romero DG, González A, Mosso LM, Lagos ET et al. Two homozygous mutations in the 11 beta-hydroxysteroid dehydrogenase type 2 gene in a case of apparent mineralocorticoid excess. J Clin Endocrinol Metab. 2003;88(6):2501–2507.Baserga M, Kaur R, Hale MA et al. Fetal growth restriction alters transcription factor binding and epigenetic mechanisms of renal 11beta-hydroxysteroid dehydrogenase type 2 in a sexspecific manner. Am J Physiol Regul Integr Comp Physiol. 2010;299: R334–342.Baserga M, Kaur R, Hale MA et al. Fetal growth restriction alters transcription factor binding and epigenetic mechanisms of renal 11beta-hydroxysteroid dehydrogenase type 2 in a sexspecific manner. Am J Physiol Regul Integr Comp Physiol. 2010;299: R334–342.Stewart PM. Cortisol as a mineralocorticoid in human disease. J Steroid Biochem Mol Biol. 1999;69(1–6):403–408.Stewart PM. Cortisol as a mineralocorticoid in human disease. J Steroid Biochem Mol Biol. 1999;69(1–6):403–408.Lee HA, Baek I, Seok YM, Yang E, Cho HM, Lee DY et al. Promoter hypomethylation upregulates Na1‑K1–2Cl- cotransporter 1 in spontaneously hypertensive rats. Biochem Biophys Res Commun. 2010;396(2):252–257.Lee HA, Baek I, Seok YM, Yang E, Cho HM, Lee DY et al. Promoter hypomethylation upregulates Na1‑K1–2Cl- cotransporter 1 in spontaneously hypertensive rats. Biochem Biophys Res Commun. 2010;396(2):252–257.Garg P, Martin CF, Elms SC, Gordon FJ, Wall SM, Garland CJ et al. Effect of the Na-K‑2Cl cotransporter NKCC1 on systemic blood pressure and smooth muscle tone. Am J Physiol Heart Circ Physiol. 2007;292(5): H2100–2105.Garg P, Martin CF, Elms SC, Gordon FJ, Wall SM, Garland CJ et al. Effect of the Na-K‑2Cl cotransporter NKCC1 on systemic blood pressure and smooth muscle tone. Am J Physiol Heart Circ Physiol. 2007;292(5): H2100–2105.Cho HM, Lee HA, Kim HY, Han HS, Kim IK. Expression of Na1‑K1–2Cl- cotransporter 1 is epigenetically regulated during postnatal development of hypertension. Am J Hypertens. 2011;24 (12):1286–1293.Cho HM, Lee HA, Kim HY, Han HS, Kim IK. Expression of Na1‑K1–2Cl- cotransporter 1 is epigenetically regulated during postnatal development of hypertension. Am J Hypertens. 2011;24 (12):1286–1293.Riviere G, Lienhard D, Andrieu T, Vieau D, Frey BM, Frey FJ. Epigenetic regulation of somatic angiotensin-converting enzyme by DNA methylation and histone acetylation. Epigenetics. 2011;6(4):478–489.Riviere G, Lienhard D, Andrieu T, Vieau D, Frey BM, Frey FJ. Epigenetic regulation of somatic angiotensin-converting enzyme by DNA methylation and histone acetylation. Epigenetics. 2011;6(4):478–489.Wang F, Demura M, Cheng Y, Zhu A, Karashima S, Yoneda T et al. Dynamic CCAAT/enhancer binding proteinassociated changes of DNA methylation in the angiotensinogen gene. Hypertension. 2014;63(2):281–288.Wang F, Demura M, Cheng Y, Zhu A, Karashima S, Yoneda T et al. Dynamic CCAAT/enhancer binding proteinassociated changes of DNA methylation in the angiotensinogen gene. Hypertension. 2014;63(2):281–288.Calhoun DA. Aldosterone and cardiovascular disease: smoke and fire. Circulation. 2006;114(24):2572–2574.Calhoun DA. Aldosterone and cardiovascular disease: smoke and fire. Circulation. 2006;114(24):2572–2574.Zhang LN, Liu PP, Wang L, Yuan F, Xu L, Xin Y et al. Lower ADD1 gene promoter DNA methylation increases the risk of essential hypertension. PLoS ONE. 2013;8(5): e63455.Zhang LN, Liu PP, Wang L, Yuan F, Xu L, Xin Y et al. Lower ADD1 gene promoter DNA methylation increases the risk of essential hypertension. PLoS ONE. 2013;8(5): e63455.Dasgupta C, Chen M, Zhang H, Yang S, Zhang L. Chronic hypoxia during gestation causes epigenetic repression of the estrogen receptor-alpha gene in ovine uterine arteries via heightened promoter methylation. Hypertension. 2012;60(3):697–704.Dasgupta C, Chen M, Zhang H, Yang S, Zhang L. Chronic hypoxia during gestation causes epigenetic repression of the estrogen receptor-alpha gene in ovine uterine arteries via heightened promoter methylation. Hypertension. 2012;60(3):697–704.Lalioti MD, Zhang J, Volkman HM, Kahle KT, Hoffmann KE, Toka HR et al. Wnk4 controls blood pressure and potassium homeostasis via regulation of mass and activity of the distal convoluted tubule. NatGenet. 2006;38(10):1124–1132.Lalioti MD, Zhang J, Volkman HM, Kahle KT, Hoffmann KE, Toka HR et al. Wnk4 controls blood pressure and potassium homeostasis via regulation of mass and activity of the distal convoluted tubule. NatGenet. 2006;38(10):1124–1132.Li C, Li Y, Li Y, Liu H, Sun Z, Lu J et al. Glucocorticoid repression of human with no lysine (K) kinase‑4 gene expression is mediated by the negative response elements in the promoter. J Mol Endocrinol. 2008;40(1):3–12.Li C, Li Y, Li Y, Liu H, Sun Z, Lu J et al. Glucocorticoid repression of human with no lysine (K) kinase‑4 gene expression is mediated by the negative response elements in the promoter. J Mol Endocrinol. 2008;40(1):3–12.Fujita T. Mechanism of salt-sensitive hypertension: focus on adrenal and sympathetic nervous systems. J Am Soc Nephrol. 2014;25(6):1148–1155.Fujita T. Mechanism of salt-sensitive hypertension: focus on adrenal and sympathetic nervous systems. J Am Soc Nephrol. 2014;25(6):1148–1155.Abrahams JM, Lenart CJ, Tobias ME. Temporal variation of induction neurogenesis in a rat model of transient middle cerebral artery occlusion. Neurol Res. 2009;31(5):528–533.Abrahams JM, Lenart CJ, Tobias ME. Temporal variation of induction neurogenesis in a rat model of transient middle cerebral artery occlusion. Neurol Res. 2009;31(5):528–533.Akechi T, Momino K, Yamashita T, Fujita T, Hayashi H, Tsunoda N et al. Contribution of problem-solving skills to fear of recurrence in breast cancer survivors. Breast Cancer Res Treat. 2014;145(1):205–210Akechi T, Momino K, Yamashita T, Fujita T, Hayashi H, Tsunoda N et al. Contribution of problem-solving skills to fear of recurrence in breast cancer survivors. Breast Cancer Res Treat. 2014;145(1):205–210Pojoga LH, Williams JS, Yao TM, Kumar A, Raffetto JD, do Nascimento GR et al. Histone demethylase LSD1 deficiency during high-salt diet is associated with enhanced vascular contraction, altered NO-cGMP relaxation pathway, and hypertension. Am J Physiol Heart Circ Physiol. 2011;301(5): H1862–871.Pojoga LH, Williams JS, Yao TM, Kumar A, Raffetto JD, do Nascimento GR et al. Histone demethylase LSD1 deficiency during high-salt diet is associated with enhanced vascular contraction, altered NO-cGMP relaxation pathway, and hypertension. Am J Physiol Heart Circ Physiol. 2011;301(5): H1862–871.Dorn LE, Watson MA, Margulies KB, Dorn GW. Reciprocal regulation of myocardial microRNAs and messenger RNA in human cardiomyopathy and reversal of the microRNA signature by biomechanical support. Circulation. 2009;119(9):1263–1271.Dorn LE, Watson MA, Margulies KB, Dorn GW. Reciprocal regulation of myocardial microRNAs and messenger RNA in human cardiomyopathy and reversal of the microRNA signature by biomechanical support. Circulation. 2009;119(9):1263–1271.Shirodkar AV, Marsden PA. Epigenetics in cardiovascular disease. Curr Opin Cardiol. 2011:26(3):209–215.Shirodkar AV, Marsden PA. Epigenetics in cardiovascular disease. Curr Opin Cardiol. 2011:26(3):209–215.Sucharov C, Bristow MR, Port JD. MiRNA expression in the failing human heart: functional correlates. J Mol Cell Cardiol. 2008;45(2):185–192.Sucharov C, Bristow MR, Port JD. MiRNA expression in the failing human heart: functional correlates. J Mol Cell Cardiol. 2008;45(2):185–192.Romero DG, Plonczynski MW, Carvajal CA, Gomez-Sanchez EP, Gomez-Sanchez CE. Microribonucleic acid‑21 increases aldosterone secretion and proliferation in H295R human adrenocortical cells. Endocrinology. 2008;149(5):2477–2483.Romero DG, Plonczynski MW, Carvajal CA, Gomez-Sanchez EP, Gomez-Sanchez CE. Microribonucleic acid‑21 increases aldosterone secretion and proliferation in H295R human adrenocortical cells. Endocrinology. 2008;149(5):2477–2483.Latronico MV, Condorelli G. MicroRNAs and cardiac pathology. Nature reviews. Cardiology. 2009;6(6):419–429.Latronico MV, Condorelli G. MicroRNAs and cardiac pathology. Nature reviews. Cardiology. 2009;6(6):419–429.Kontaraki JE, Marketou ME, Zacharis EA, Parthenakis FI, Vardas PE. Differential expression of vascular smooth musclemodulating microRNAs in human peripheral blood mononuclear cells: novel targets in essential hypertension. J Hum Hypertens. 2013;28(8):510–516.Kontaraki JE, Marketou ME, Zacharis EA, Parthenakis FI, Vardas PE. Differential expression of vascular smooth musclemodulating microRNAs in human peripheral blood mononuclear cells: novel targets in essential hypertension. J Hum Hypertens. 2013;28(8):510–516.Marques FZ, Campain AE, Tomaszewski M, Zukowska-Szczechowska E, Yang YH, Charchar FJ et al. Gene expression profiling reveals renin mRNA overexpression in human hypertensive kidneys and a role for microRNAs. Hypertension. 2011;58 (6):1093–1098.Marques FZ, Campain AE, Tomaszewski M, Zukowska-Szczechowska E, Yang YH, Charchar FJ et al. Gene expression profiling reveals renin mRNA overexpression in human hypertensive kidneys and a role for microRNAs. Hypertension. 2011;58 (6):1093–1098.Jiang Q, Lagos-Quintana M, Liu D, Shi Y, Helker C, Herzog W et al. miR‑30a regulates endothelial tip cell formation and arteriolar branching. Hypertension. 2013;62(3):592–598.Jiang Q, Lagos-Quintana M, Liu D, Shi Y, Helker C, Herzog W et al. miR‑30a regulates endothelial tip cell formation and arteriolar branching. Hypertension. 2013;62(3):592–598.Batista1 PJ, Chang HY. Long Noncoding RNAs. Cell Address Codes Develop Dis Cell. 2013;152(6):1298–1307.Batista1 PJ, Chang HY. Long Noncoding RNAs. Cell Address Codes Develop Dis Cell. 2013;152(6):1298–1307.Bannister AJ, Kouzarides T. Reversing histone methylation. Nature. 2005;436(7054):1103–1106.Bannister AJ, Kouzarides T. Reversing histone methylation. Nature. 2005;436(7054):1103–1106.Bannister AJ, Kouzarides T. Regulation of chromatin by histone modifications. Cell Res. 2011;21(3):381–395.Bannister AJ, Kouzarides T. Regulation of chromatin by histone modifications. Cell Res. 2011;21(3):381–395.Friso S, Pizzolo F, Choi SW, Guarini P, Castagna A, Ravagnani V et al. Epigenetic control of 11 betahydroxysteroid dehydrogenase 2 gene promoter is related to human hypertension. Atherosclerosis. 2008;199(2):323–327.Friso S, Pizzolo F, Choi SW, Guarini P, Castagna A, Ravagnani V et al. Epigenetic control of 11 betahydroxysteroid dehydrogenase 2 gene promoter is related to human hypertension. Atherosclerosis. 2008;199(2):323–327.Sober S, Laan M, Annilo T. MicroRNAs miR‑124 and miR‑135a are potential regulators of the mineralocorticoid receptor gene (NR3C2) expression. Biochem Biophys Res Commun. 2010;391(1):727–732.Sober S, Laan M, Annilo T. MicroRNAs miR‑124 and miR‑135a are potential regulators of the mineralocorticoid receptor gene (NR3C2) expression. Biochem Biophys Res Commun. 2010;391(1):727–732.Di Castro S, Scarpino S, Marchitti S, Bianchi F, Stanzione R, Cotugno M et al. Differential modulation of uncoupling protein 2 in kidneys of stroke-prone spontaneously hypertensive rats under highsalt/ low-potassium diet. Hypertension. 2013;61(2):534–541.Di Castro S, Scarpino S, Marchitti S, Bianchi F, Stanzione R, Cotugno M et al. Differential modulation of uncoupling protein 2 in kidneys of stroke-prone spontaneously hypertensive rats under highsalt/ low-potassium diet. Hypertension. 2013;61(2):534–541.Ling S, Nanhwan M, Qian J, Kodakandla M, Castillo AC, Thomas B et al. Modulation of microRNAs in hypertension-induced arterial remodeling through the beta1 and beta3‑adrenoreceptor pathways. J Mol Cell Cardiol. 2013;65:127–136.Ling S, Nanhwan M, Qian J, Kodakandla M, Castillo AC, Thomas B et al. Modulation of microRNAs in hypertension-induced arterial remodeling through the beta1 and beta3‑adrenoreceptor pathways. J Mol Cell Cardiol. 2013;65:127–136.Jackson KL, Marques FZ, Watson AM, Palma-Rigo K, Nguyen-Huu TP, Morris BJ et al. A novel interaction between sympathetic overactivity and aberrant regulation of renin by miR‑181a in BPH/2J genetically hypertensive mice. Hypertension. 2013;62(4):775–781.Jackson KL, Marques FZ, Watson AM, Palma-Rigo K, Nguyen-Huu TP, Morris BJ et al. A novel interaction between sympathetic overactivity and aberrant regulation of renin by miR‑181a in BPH/2J genetically hypertensive mice. Hypertension. 2013;62(4):775–781.Sethupathy P, Borel C, Gagnebin M, Grant GR, Deutsch S, Elton TS et al. Human microRNA- 155 on chromosome 21 differentially interacts with its polymorphic target in the AGTR1 3’ untranslated region: a mechanism for functional singlenucleotide polymorphisms related to phenotypes. Am J Hum Genet. 2007;81(2):405–413.Sethupathy P, Borel C, Gagnebin M, Grant GR, Deutsch S, Elton TS et al. Human microRNA- 155 on chromosome 21 differentially interacts with its polymorphic target in the AGTR1 3’ untranslated region: a mechanism for functional singlenucleotide polymorphisms related to phenotypes. Am J Hum Genet. 2007;81(2):405–413.Robertson S, MacKenzie SM, Alvarez-Madrazo S, Diver LA, Lin J, Stewart PM et al. MicroRNA‑24 is a novel regulator of aldosterone and cortisol production in the human adrenal cortex. Hypertension. 2013;62(3):572–528.Robertson S, MacKenzie SM, Alvarez-Madrazo S, Diver LA, Lin J, Stewart PM et al. MicroRNA‑24 is a novel regulator of aldosterone and cortisol production in the human adrenal cortex. Hypertension. 2013;62(3):572–528.

The authors declare that there are no conflicts of interest present.