Skip to main content

Advertisement

Log in

Unravelling the Lesser Known Facets of Angiotensin II Type 1 Receptor

  • Hypertension and the Kidney (RM Carey, Section Editor)
  • Published:
Current Hypertension Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Hypertension is an important risk factor in various pathologies. Despite enormous advancements in health sciences, the number of hypertensive individuals is increasing worldwide. The complex interplay between genetic and epigenetic factors seems to be a promising pathway to exploring the pathophysiology of hypertension.

Recent Findings

Various single gene and genome wide association studies have generated huge but non-reproducible data that highlights the role of some additional but as yet unidentified factor(s) in disease outcome. Dietary pattern and epigenetic mechanism (mainly DNA methylation) have shown a profound effect on blood pressure regulation. Angiotensin II and its receptors are known to play an important role in maintaining blood pressure; hence, a larger section of antihypertensive drugs targets the renin–angiotensin system (RAS). Angiotensin II type 1 receptor (AT1R), besides maintaining blood pressure, also has a role in cancer progression.

Summary

Besides other pathways, RAS still remains the main player in blood pressure regulation. Additionally, AT1R has recently emerged as a molecule with diverse roles ranging from physiologic to cancer progression.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • of importance •• of major importance

  1. Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension: analysis of worldwide data. Lancet. 2005;365:217–23. doi:10.1016/S0140-6736(05)17741-1.

    Article  PubMed  Google Scholar 

  2. Das SK, Sanyal K, Basu A. Study of urban community survey in India: growing trend of high prevalence of hypertension in a developing country. Int J Med Sci. 2005;2:70–8.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Cowley AW. The genetic dissection of essential hypertension. Nat Rev Genet. 2006;7(11):829–40. doi:10.1038/nrg1967.

    Article  CAS  PubMed  Google Scholar 

  4. • Shamieh SE, Siest VS. Genetic biomarkers of hypertension and future challenges integrating epigenomics. Clin Chim Acta. 2012;414:259–65. doi:10.1016/j.cca.2012.09.018. This review highlights candidate genes of metabolic pathways other than RAS involved in blood pressure regulation

    Article  PubMed  Google Scholar 

  5. Natekar A, Olds RL, Lau MW, Min K, Imoto K, Slavin TP. Elevated blood pressure: our family’s fault? The genetics of essential hypertension. World J Cardiol. 2014;6(5):327–37. doi:10.4330/wjc.v6.i5.327.

    PubMed  PubMed Central  Google Scholar 

  6. • Cuddy MLS. Treatment of hypertension: guidelines from JNC 7 (Seventh report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure). J Prac Nurs. 2005;55(4):17–23. This is JNC VII report having complete description about diagnosis, detection and treatment of high blood pressure

    Google Scholar 

  7. Hackenthal E, Paul M, Ganten D, Taugner R. Morphology, physiology and molecular biology of renin secretion. Physiol Rev. 1990;70(4):1067–116.

    CAS  PubMed  Google Scholar 

  8. • Lavoie JL, Sigmund CD. Minireview: overview of the renin-angiotensin system—an endocrine and paracrine system. Endocrinology. 2003;144(6):2179–83. doi:10.1210/en.2003-0150. This mini review describes the importance of paracrine (tissue RAS) in addition to the conventional endocrine RAS. Paper also includes detail of transgenic animal models of tissue RAS

    Article  CAS  PubMed  Google Scholar 

  9. Dinh DT, Frauman AG, Johnston CI, Fabiani ME. Angiotensin receptors: distribution, signalling and function. Clin Sci (Lond). 2001;100(5):481–92. doi:10.1042/cs1000481.

    Article  CAS  Google Scholar 

  10. Berka JLW, Agrotis A, Deliyanti D. The retinal renin-angiotensin system: roles of angiotensin II and aldosterone. Peptides. 2012;36(1):142–50. doi:10.1016/j.peptides.2012.04.008.

    Article  Google Scholar 

  11. Saavedra JM, Angiotensin II. AT(1) receptor blockers as treatments for inflammatory brain disorders. Clin Sci (Lond). 2012;123(10):567–90. doi:10.1042/CS20120078.

    Article  CAS  Google Scholar 

  12. Owens GK. Influence of blood pressure on development of aortic medial smooth muscle hypertrophy in spontaneously hypertensive rats. Hypertension. 1987;9(2):178–87.

    Article  CAS  PubMed  Google Scholar 

  13. Peach MJ. Renin-angiotensin system: biochemistry and mechanisms of action. Physiol Rev. 1977;57(2):313–70.

    CAS  PubMed  Google Scholar 

  14. Weber H, Taylor DS, Molly CJ. Angiotensin II induces delayed mitogenesis and cellular proliferation in rat aortic smooth muscle cells. J Clin Invest. 1994;93(2):788–98. doi:10.1172/JCI117033.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Schorb W, Booz GW, Dostal DE, Conrad KM, Chang KC, Baker KM. Angiotensin II is mitogenic in neonatal rat cardiac fibroblasts. Circ Res. 1993;72(6):1245–54. doi:10.1161/01.RES.72.6.1245.

    Article  CAS  PubMed  Google Scholar 

  16. Dostal DE, Hunt RA, Kule CE, Bhat GJ, Karoor V, McWhinney CD, et al. Molecular mechanisms of angiotensin II in modulating cardiac function: intracardiac effects and signal transduction pathways. J Mol Cell Cardiol. 1997;29(11):2893–902.

    Article  CAS  PubMed  Google Scholar 

  17. Bugno M, Graeve L, Gatsios P, Koi A, Heinrich PC, Travis J, et al. Identification of the interleukin-6/oncostatin M response element in the rat tissue inhibitor of metalloproteinases-1 (TIMP-1) promoter. Nucleic Acids Res. 1995;23(24):5041–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Deng J, Wang DX, Deng W, Li CY, Tong J. The effect of endogenous angiotensin II on alveolar fluid clearance in rats with acute lung injury. Can Respir J. 2012;19(5):311–8.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Pena C, Fonseca HJP, Rincon J, Pedreanez A, Viera N, Mosquera J. Pro-inflammatory role of angiotensin II in mercuric chloride induced nephropathy in rats. J Immunotoxicol. 2013;10(2):125–32. doi:10.3109/1547691X.2012.699478.

    Article  CAS  PubMed  Google Scholar 

  20. Mendelsohn FA. Localization and properties of angiotensin receptors. J Hypertens. 1985;3(4):307–16.

    Article  CAS  PubMed  Google Scholar 

  21. •• Chow BSM, Allen TJ. Angiotensin II type 2 receptor (AT2R) in renal and cardiovascular disease. Clin Sci. 2016;130(15):1307–26. doi:10.1042/CS20160243. This review describes AT2R properties along with its renal and cardiovascular role in great depth

    Article  CAS  PubMed  Google Scholar 

  22. Clauser E. Molecular structure and function of angiotensin II receptors. Nephrologie. 1998;19(7):403–10.

    CAS  PubMed  Google Scholar 

  23. Elton TS, Stephan CC, Taylor GR, Kimball MG, Martin MM, Durand JN, et al. Isolation of two distinct type 1 angiotensin II receptor genes. Biochem Biophys Res Commun. 1992;184(2):1067–73. doi:10.1016/0006-291X(92)90700-U.

    Article  CAS  PubMed  Google Scholar 

  24. Su B, Martin MM, Beason KB, Miller PJ, Elton TS. The genomic organization and functional analysis of the promoter for the human angiotensin II type 1 receptor. Biochem Biophys Res Commun. 1994;204(3):1039–46. doi:10.1006/bbrc.1994.2567.

    Article  CAS  PubMed  Google Scholar 

  25. • Elton TS, Martin MM. Alternative splicing: a novel mechanism to fine tune the expression and function of the human AT1 receptor. Trends Endocrinol Metabol. 2003;14(2):66–71. doi:10.1016/S1043-2760(02)00038-3. This article details about different transcript(s) formation through alternate splicing and their functional significance

    Article  CAS  Google Scholar 

  26. Guo DF, Furuta H, Mizukoshi M, Inagami T. The genomic organization of human angiotensin II type 1 receptor. Biochem Biophys Res Commun. 1994;200(1):313–9. doi:10.1006/bbrc.1994.1450.

    Article  CAS  PubMed  Google Scholar 

  27. •• Zhang H, Unal H, Gati C, Han GW, Liu W, Zatsepin NA, et al. Structure of the angiotensin receptor revealed by serial femtosecond crystallography. Cell. 2015;161(4):833–44. doi:10.1016/j.cell.2015.04.011. This paper is the first to report details of crystal structure of human AT1R in complex with selective antagonist

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. •• Zhang H, Unal H, Desnoyer R, Han GW, Patel N, Katritch V, et al. Structural basis for ligand recognition and functional selectivity at angiotensin receptor. J Biol Chem. 2015;290(49):29127–39. doi:10.1074/jbc.M115.689000. This article is further extension of work on crystal structure of AT1R highlighting role of specific amino acid residues of AT1R on its peptide binding efficiency

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Zhang X, Edrmann J, Regitz ZV, Kurzinger S, Hense HW, Schunkert H. Evaluation of three polymorphisms in the promoter region of the angiotensin II type 1 receptor gene. J Hypertens. 2000;18(3):267–72.

    Article  CAS  PubMed  Google Scholar 

  30. Wei J, Yan L, Hui SH, Lin J, Yun SY, Qi H, et al. Single nucleotide polymorphisms in promoter of angiotensin II type 1 receptor gene associated with essential hypertension and coronary heart disease in Chinese population. Acta Pharmacol Sin. 2003;24(11):1083–8.

    Google Scholar 

  31. Su S, Chen J, Zhao J, Huang J, Wang X, Chen R, et al. Angiotensin II type 1 receptor gene and myocardial infarction: tagging SNPs and haplotype based association study. Pharmacogenetics. 2004;14(10):673–81.

    Article  CAS  PubMed  Google Scholar 

  32. Zhang KX, Liu TB, Xu QX, Zhu DL, Huang W. Association of angiotensin II receptor type 1 gene single nucleotide polymorphism with Chinese essential hypertension complicated with coronary heart disease. Zhonghua Xin Xue Guan Bing Za Zhi. 2005;33(8):720–3.

    CAS  PubMed  Google Scholar 

  33. Su SL, Lu KC, Lin YF, Hsu YJ, Lee PY, Yang HY, et al. Gene polymorphisms of angiotensin converting enzyme and angiotensin II type 1 receptor among chronic kidney disease patients in Chinese population. J Renin-Angiotensin-Aldosterone Syst. 2012;13(1):148–54. doi:10.1177/1470320311430989.

    Article  CAS  PubMed  Google Scholar 

  34. Assareh AA, Mather KA, Crawford JD, Wen W, Anstey KJ, Easteal S, et al. Renin-angiotensin system genetic polymorphisms and brain white matter lesions in older Australians. Am J Hypertens. 2014;27(9):1191–8. doi:10.1093/ajh/hpu035.

    Article  PubMed  Google Scholar 

  35. Patnaik M, Pati P, Swain SN, Mohapatra MK, Dwibedi B, Kar SK, et al. Aldosterone synthase C-344 T, angiotensin II type 1 receptor A1166C and 11-β hydroxysteroid dehydrogenase G534A gene polymorphisms and essential hypertension in the population of Odisha. India J Genet. 2014;93(3):799–808.

    Article  CAS  PubMed  Google Scholar 

  36. Szolnoki Z, Havasi V, Talian G, Bene J, Komlosi K, Somogyvari F, et al. Angiotensin II type 1 receptor A1166C polymorphism is associated with increased risk of ischemic stroke in hypertensive smokers. J Mol Neurosci. 2006;28(3):285–90. doi:10.1385/JMN:28:3:285.

    Article  CAS  PubMed  Google Scholar 

  37. Smilde TD, Zuurman MW, Hillege HL, Veldhuisen DJ, Gilst WH, Steege G, et al. Renal function dependent association of AGTR1 polymorphism (A1166C) and electrocardiographic left-ventricular hypertrophy. Am J Hypertens. 2007;20(10):1097–103. doi:10.1016/j.amjhyper.2007.04.023.

    Article  CAS  PubMed  Google Scholar 

  38. Kondo DJ, Speer MC, Krishnan KR, McQuoid DR, Slifer SH, Pieper CF, et al. Association of AGTR1 with 18-month treatment outcome in late-life depression. Am J Geriatr Psychiatry. 2007;15(7):564–72. doi:10.1097/JGP.0b013e31805470a4.

    Article  PubMed  Google Scholar 

  39. Shah VN, Cheema BS, Sharma R, Khullar M, Kohli HS, Ahluwali TS, et al. ACAC beta gene (rs2268388) and AGTR1 gene (rs5186) polymorphism and the risk of nephropathy in Asian Indian patients with type 2 diabetes. Mol Cell Biochem. 2013;372(1–2):191–8. doi:10.1007/s11010-012-1460-2.

    Article  CAS  PubMed  Google Scholar 

  40. Jones GT, Thompson AR, Bockxmeer FM, Hafez H, Cooper JA, Golledge J, et al. Angiotensin II type 1 receptor 1166C polymorphism is associated with abdominal aortic aneurysm in three independent cohorts. Arterioscler Thromb Vasc Biol. 2008;28(4):764–70. doi:10.1161/ATVBAHA.107.155564.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Wu CK, Tsai CT, Chang YC, Luo JL, Wang YC, Hwang JJ, et al. Genetic polymorphisms of the angiotensin II type 1 receptor gene and diastolic heart failure. J Hypertens. 2009;27(3):502–7.

    Article  CAS  PubMed  Google Scholar 

  42. Jira M, Zavodna E, Honzikova N, Novakova Z, Vasku A, Holla IL, et al. Association of A1166C polymorphism in AT(1) receptor gene with baroreflex sensitivity. Physiol Res. 2010;59(4):517–28.

    CAS  PubMed  Google Scholar 

  43. Turgut S, Akin F, Akcilar R, Ayada C, Turgut G. Angiotensin converting enzyme I/D, angiotensinogen M235T and AT1-R A/C 1166 gene polymorphisms in patients with acromegaly. Mol Biol Rep. 2011;38(1):569–76. doi:10.1007/s11033-010-0142-y.

    Article  CAS  PubMed  Google Scholar 

  44. Kelly M, Bagnall RD, Peverill RE, Donelan L, Corben L, Delatycki MB, et al. A polymorphic miR-155 binding site in AGTR1 is associated with cardiac hypertrophy in Friedreich ataxia. J Mol Cell Cardiol. 2011;51(5):848–54. doi:10.1016/j.yjmcc.2011.07.001.

    Article  CAS  PubMed  Google Scholar 

  45. Kaur R, Das R, Ahluwalia J, Kumar RM, Talwar KK. Synergistic effect of angiotensin II type 1 receptor 1166 A/C with angiotensin converting enzyme polymorphism on risk of acute myocardial infarction in north Indians. J Renin-Angiotensin-Aldosterone Syst. 2012;13(4):440–5.

    Article  PubMed  Google Scholar 

  46. Sousa JMA, Rodriguez FA, Heredia M, Tamayo E, Fulgencio GM, Lajo C, et al. Genetic polymorphisms located in TGFB1, AGTR1 and VEGFA genes are associated to chronic renal allograft dysfunction. Cytokine. 2012;58(3):321–6. doi:10.1016/j.cyto.2012.02.017.

    Article  Google Scholar 

  47. Jin Y, Kuznetsova T, Thijs L, Schmitz B, Liu Y, Asayama K, et al. Association of left ventricular mass with the AGTR1 A1166C polymorphism. Am J Hypertens. 2012;25(4):472–8. doi:10.1038/ajh.2011.244.

    Article  CAS  PubMed  Google Scholar 

  48. Tian J, Hu S, Wang F, Yang X, Li Y, Huang C. PPARG, AGTR1, CXCL 16 and LGAL S2 polymorphisms are correlated with the risk for coronary heart disease. Int J Clin Exp Pathol. 2015;8(3):3138–43.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Pousada G, Baloira A, Valverde D. Molecular and clinical analysis of TRPC6 and AGTR1 genes in patients with pulmonary arterial hypertension. Orphanet J Rare Dis. 2015;10:1. doi:10.1186/s13023-014-0216-3.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Kaczmarczyk M, Kuprjanowicz A, Loniewska B, Goracy I, Taryma LO, Skonieczna ZK, et al. Epistatic interaction between common AGT G(-6)A (rs5051) and AGTR1 A1166C (rs5186) variants contributes to variation in kidney size at birth. Gene. 2015;572(1):72–8. doi:10.1016/j.gene.2015.06.071.

    Article  CAS  PubMed  Google Scholar 

  51. Campbell CY, Fang BF, Guo X, Peralta CA, Psaty BM, Rich SS, et al. Association between genetic variants in the ACE, AGT, AGTR1 and AGTR2 genes and renal function in the multi-ethnic study of atherosclerosis. Am J Nephrol. 2010;32(2):156–62. doi:10.1159/000315866.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Taylor WD, Benjamin S, McQuoid DR, Payne ME, Krishnan RR, MacFall JR, et al. AGTR1 gene variation: association with depression and frontotemporal morphology. Psychiatry Res. 2012;202(2):104–9. doi:10.1016/j.pscychresns.2012.03.007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Zain SM, Mohamed Z, Mahadeva S, Rampal S, Basu RC, Cheah PL, et al. Susceptibility and gene interaction study of the angiotensin II type 1 receptor (AGTR1) gene polymorphisms with non-alcoholic fatty liver disease in a multi-ethnic population. PLoS One. 2013;8(3):e58538. doi:10.1371/journal.pone.0058538.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Ji L, Cai X, Zhang L, Fei L, Wang L, Su J, et al. Association between polymorphisms in the renin-angiotensin-aldosterone system genes and essential hypertension in the Han Chinese population. PLoS One. 2013;8(8):e72701. doi:10.1371/journal.pone.0072701.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Haas U, Sczakiel G, Laufer SD. MicroRNA-mediated regulation of gene expression is affected by disease associated SNPs within the 3′-UTR via altered RNA structure. RNA Biol. 2012;9(6):924–37. doi:10.4161/rna.20497.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Zhou TB, Jiang ZP, Zhou JF, Zhang YM. Association of angiotensin II type 1 receptor A1166C gene polymorphism with the susceptibility of immunoglobulin IgA nephropathy. Ren Fail. 2015;37(3):359–62. doi:10.3109/0886022X.2014.1000800.

    Article  CAS  PubMed  Google Scholar 

  57. Mao S, Huang S. Lack of association of angiotensin II type 1 receptor A1166C gene polymorphism with the risk of end-stage renal disease. Ren Fail. 2013;35(9):1295–301. doi:10.3109/0886022X.2013.820663.

    Article  CAS  PubMed  Google Scholar 

  58. Hulyam K, Aysegul B, Veysi GH, Demet O, Irfan D, Ertugrul C, et al. Frequency of angiotensin II type 1 receptor gene polymorphism in Turkish acute stroke patients. J Cell Mol Med. 2013;17(4):475–81. doi:10.1111/jcmm.12017.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Zhao L, Dewan AT, Bracken MB. Association of maternal AGTR1 polymorphisms and preeclampsia: a systematic review and meta-analysis. J Matern Fetal Neonatal Med. 2012;25(12):2676–80. doi:10.3109/14767058.2012.708370.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Srivastava S, Bhagi S, Kumari B, Chandra K, Sarkar S, Ashraf MZ. Association of polymorphisms in angiotensin and aldosterone synthase genes of the renin-angiotensin-aldosterone system with high-altitude pulmonary edema. J Renin-Angiotensin-Aldosterone Syst. 2012;13(1):155–60. doi:10.1177/1470320311430990.

    Article  CAS  PubMed  Google Scholar 

  61. Sticchi E, Romagnuolo I, Sofi F, Pratesi G, Pulli R, Pratesi C, et al. Association between polymorphisms of the renin angiotensin system and carotid stenosis. J Vasc Surg. 2011;54(2):467–73. doi:10.1016/j.jvs.2011.01.039.

    Article  PubMed  Google Scholar 

  62. Koehle MS, Wang P, Guenette JA, Rupert JL. No association between variants in the ACE and angiotensin II type 1 receptor genes and acute mountain sickness in Nepalese pilgrims to the Janai Purnima Festival at 4380 m. High Alt Med Biol. 2006;7(4):281–9. doi:10.1089/ham.2006.7.281.

    Article  CAS  PubMed  Google Scholar 

  63. Chou HT, Shi YR, Wu JY, Tsai FG. Angiotensin II type 1 receptor gene adenine/cytosine 1166 polymorphism is not associated with mitral valve prolapse syndrome in Taiwan Chinese. Circ J. 2002;66(2):163–6.

    Article  CAS  PubMed  Google Scholar 

  64. Sugimoto K, Katsuya T, Ohkubo T, Hozawa A, Yamamoto K, Matsuo A, et al. Association between angiotensin II type 1 receptor gene polymorphism and essential hypertension: the Ohasama study. Hypertens Res. 2004;27(8):551–6.

    Article  CAS  PubMed  Google Scholar 

  65. Shahin DS, Irshaid YM, Saleh AA. The A(1166)C polymorphism of AT1R gene is associated with an early onset of hypertension and high waist circumference in Jordanian males attending the Jordan University Hospital. Clin Exp Hypertens. 2014;36(5):333–9.

    Article  CAS  PubMed  Google Scholar 

  66. Chandra S, Narang R, Sreenivas V, Bhatia J, Saluja D, Srivastava K. Association of angiotensin II type 1 receptor (A1166C) gene polymorphism and its increased expression in essential hypertension: a case-control study. PLoS One. 2014;9(7):e101502. doi:10.1371/journal.pone.0101502.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Singh DK, Jajodia A, Kaur H, Kukreti R, Karthikeyan M. Gender specific association of RAS gene polymorphism with essential hypertension: a case-control study. Biomed Res Int. 2014;538053 doi:10.1155/2014/538053.

  68. Widiker S, Karst S, Wagener A, Brockmann GA. High fat diet leads to a decreased methylation of the Mc4r gene in the obese BFMI and the lean B6 mouse lines. J Appl Genet. 2010;51(2):193–7. doi:10.1007/BF03195727.

    Article  CAS  PubMed  Google Scholar 

  69. • Choi SW, Friso S. Epigenetics: a new bridge between nutrition and health. Adv Nutr. 2010;1(1):8–16. doi:10.3945/an.110.1004. This review article describes the effect of nutrients (e.g., folate) and bioactive food components (e.g., tea polyphenols, isothiocynates) on DNA methylation. Paper also describes various epigenetic mechanisms in addition to nucleosome and chromatin structure

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Bogdarina I, Welham S, King PJ, Burns SP, Clark AJ. Epigenetic modification of the renin angiotensin system in the fetal programming of hypertension. Circ Res. 2007;100(4):520–6. doi:10.1161/01.RES.0000258855.60637.58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. •• Xiao D, Dasgupta C, Li Y, Huang X, Zhang L. Perinatal nicotine exposure increases angiotensin II receptor mediated vascular contractility in adult offspring. PLoS One. 2014;9(9):e108161. doi:10.1371/journal.pone.0108161. The paper provides experimental evidence of novel mechanism of selectively altered methylation of specific CpG at AT1R/AT2R in the developing vasculature and resultant increase in vascular contractility caused by perinatal nicotine exposure

    Article  PubMed  PubMed Central  Google Scholar 

  72. Pei F, Wang X, Yue R, Chen C, Huang J, Li X, et al. Differential expression and DNA methylation of angiotensin type 1A receptors in vascular tissues during genetic hypertension development. Mol Cell Biochem. 2015;402(1–2):1–8. doi:10.1007/s11010-014-2295-9.

    Article  CAS  PubMed  Google Scholar 

  73. Lee HA, Baek I, Seok YM, Yang E, Cho HM, Lee DY, et al. Promoter hypomethylation upregulates Na+-K+-2Cl- cotransporter 1 in spontaneously hypertensive rats. Biochem Biophys Res Commun. 2010;396(2):252–7. doi:10.1016/j.bbrc.2010.04.074.

    Article  CAS  PubMed  Google Scholar 

  74. •• Riviere G, Lienhard G, 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):478–89. This article examines role of epigenetic mechanisms on the control of somatic ACE expression both in vitro and in vivo. Methodology involving bisulphite sequencing, RT-qPCR and well-designed strategy was able to indicate strong influence of such mechanisms on ACE expression

    Article  CAS  PubMed  Google Scholar 

  75. Wang X, Falkner B, Zhu H, Shi H, Su S, Xu X, et al. A genome wide methylation study on essential hypertension in young African American males. PLoS One. 2013;8(1):e53938. doi:10.1371/journal.pone.0053938.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. 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):149–55.

    Google Scholar 

  77. Kulkarni A, Chavan GP, Mehendale S, Yadav H, Joshi S. Global DNA methylation patterns in placenta and its association with maternal hypertension in pre-eclampsia. DNA Cell Biol. 2011;30(2):79–84. doi:10.1089/dna.2010.1084.

    Article  CAS  PubMed  Google Scholar 

  78. Kato N, Loh M, Takeuchi F, Verweji N, Wang X, Zhang W, et al. Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicated a role for DNA methylation. Nat Genet. 2015;47(11):1282–93. doi:10.1038/ng.3405.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Koopaei AR, Fouladkou F, Frey FJ, Frey BM. Epigenetic regulation of 11-beta hydroxysteroid dehydrogenase type 2 expression. J Clin Invest. 2004;114(8):1146–57. doi:10.1172/JCI21647.

    Article  Google Scholar 

  80. Zhang LN, Liu PP, Wang L, Yuan F, Xu L, Xin Y, et al. Lower ADD1gene promoter DNA methylation increases the risk of essential hypertension. PLoS One. 2013;8(5):e63455. doi:10.1371/journal.pone.0063455.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Fan R, Wang WJ, Zhong QL, Duan SW, Xu XT, Hao LM, et al. Aberrant methylation of GCK gene body is associated with the risk of essential hypertension. Mol Med Rep. 2015;12(2):2390–4. doi:10.3892/mmr.2015.3631.

    CAS  PubMed  Google Scholar 

  82. •• Fan R, Mao S, Zhong F, Gong M, Yin F, Hao L, et al. Association of AGTR1 promoter methylation levels with essential hypertension risk: a matched case-control study. Cytogenet Genome Res. 2015;147(2–3):95–102. doi:10.1159/000442366. This is the first paper to investigate correlation of AT1R methylation with risk of EH in humans. Article also includes correlation between methylation and other clinical indicators

    Article  PubMed  Google Scholar 

  83. Azevedo H, Fujita A, Bando SY, Lamashita P, Filho MCA. Transcriptional network analysis reveals that AT1 and AT2 angiotensin II receptors are both involved in the regulation of genes essential for glioma progression. PLoS One. 2014;9(11):e110934. doi:10.1371/journal.pone.0110934.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Childers WK. Interactions of the renin-angiotensin system in colorectal cancer and metastasis. Int J Color Dis. 2015;30(6):749–52. doi:10.1007/s00384-014-2118-1.

    Article  Google Scholar 

  85. Arrieta O, Garza VC, Vizcaino G, Pineda B, Pedro HN, Salazar GP, et al. Association between AT1 and AT2 angiotensin II receptor expression with cell proliferation and angiogenesis in operable breast cancer. Tumor Biol. 2015;36(7):5627–34. doi:10.1007/s13277-015-3235-3.

    Article  CAS  Google Scholar 

  86. Chen X, Meng Q, Zhao Y, Liu M, Li D, Yang Y, et al. Angiotensin II type 1 receptor antagonists inhibit cell proliferation and angiogenesis in breast cancer. Cancer Lett. 2013;328(2):318–24. doi:10.1016/j.canlet.2012.10.006.

    Article  CAS  PubMed  Google Scholar 

  87. Oh E, Kim JY, Cho Y, An H, Lee N, Jo H, et al. Overexpression of angiotensin II type 1 receptor in breast cancer cells induces epithelial-mesenchymal transition and promotes tumor growth and angiogenesis. Biochim Biophys Acta. 1863;2016:1071–81. doi:10.1016/j.bbamcr.2016.03.010.

    Google Scholar 

  88. Salata C, Machado SCF, Mencalha AL, Andrade CB, Campos VM, Lacerda MCA, et al. Chemotherapy and radiation regimes to breast cancer treatment induce changes in mRNA levels of renin-angiotensin system related genes in cardiac tissue. J Renin-Angiotensin-Aldosterone Syst. 2012;14(4):330–6.

    Article  PubMed  Google Scholar 

  89. Bi FF, Li D, Cao C, Li CY, Yang Q. Regulation of angiotensin II type 1 receptor expression in ovarian cancer: a potential role of BRCA1. J Ovarian Res. 2013;6(1):89. doi:10.1186/1757-2215-6-89.

    Article  PubMed  PubMed Central  Google Scholar 

  90. Fishchuk LE, Gorovenko NG. Genetic polymorphisms of the renin angiotensin system in breast cancer patients. Exp Oncol. 2013;35(2):101–4.

    CAS  PubMed  Google Scholar 

  91. Guo R, Gu J, Zhang Z, Wang Y, Gu C. MicroRNA-410 functions as a tumor suppressor by targeting angiotensin II type 1 receptor in pancreatic cancer. IUBMB Life. 2015;67(1):42–53. doi:10.1002/iub.1342.

    Article  CAS  PubMed  Google Scholar 

  92. Zhou L, Luo Y, Sato S, Tanabe E, Kitayoshi M, Fujiwara R, et al. Role of two types of angiotensin II receptors in colorectal carcinoma progression. Pathobiology. 2014;81(4):169–75. doi:10.1159/000362092.

    Article  CAS  PubMed  Google Scholar 

  93. Fan L, Feng Y, Wan HY, Ni L, Qian YR, Guo Y, et al. Hypoxia induces dysregulation of local renin-angiotensin system in mouse Lewis lung carcinoma cells. Genet Mol Res. 2014;13(4):10562–73. doi:10.4238/2014.

    Article  CAS  PubMed  Google Scholar 

  94. Takahashi S, Uemura H, Seeni A, Tang M, Komiya M, Long N, et al. Therapeutic targeting of angiotensin II receptor type 1 to regulate androgen receptor in prostate cancer. Prostate. 2012;72(14):1559–72. doi:10.1002/pros.22505.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors are thankful to the institute for providing all the infrastructure and required permissions to carry out this work at Department cum National Centre for Human Genome Studies and Research (NCHGSR). A financial grant in the form of DBT fellowship (DBT-JRF) by the Department of Biotechnology, Ministry of Science and Technology, Government of India, to Mayank Chaudhary is also thankfully acknowledged.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Shashi Chaudhary.

Ethics declarations

Conflict of Interest

The authors declare no conflicts of interest.

Human and Animal Rights and Informed Consent

None of the authors performed any studies on human or animal subjects for this review article.

Additional information

This article is part of the Topical Collection on Hypertension and the Kidney

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chaudhary, M., Chaudhary, S. Unravelling the Lesser Known Facets of Angiotensin II Type 1 Receptor. Curr Hypertens Rep 19, 1 (2017). https://doi.org/10.1007/s11906-017-0699-0

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11906-017-0699-0

Keywords

Navigation