Comparative analysis of relative gene expression data reveals novel microRNAs in the artery of rats with renovascular hypertension
Keywords:Renovascular hypertension, 2-kidney-1-clip, Vascular endothelial function, MicroRNAs expression profiling
- The regulatory mechanisms of vascular dysfunction in rats with renovascular hypertension are poorly understood.
- MiRNA sequencing was performed to investigate the gene regulatory pathways associated with vascular dysfunction in rats with renovascular hypertension.
- We identified 17 miRNAs that were differentially expressed. These miRNAs were associated with immune-inflammatory and metabolic pathways involved in vascular dysfunction. Treatment with losartan maintained their expression and the levels of cytokines.
- Our results provide valuable information on mechanisms of miRNA-mediated vascular function regulation in 2K1C rats with renovascular hypertension.
Abstract: Hypertension is associated with impaired vascular endothelial function. However, the regulatory mechanisms of vascular dysfunction in rats with renovascular hypertension (RVH) remain poorly understood. In this study, the 2-kidney-1-clip (2K1C) hypertensive rat model was utilized. Next-generation sequencing was then used to detect microRNA (miRNA) expression profiling in the arteries of 2K1C rats. We identified 17 miRNAs that were differentially expressed in the 2K1C group compared with the sham group, of which 9 were downregulated and 8 were upregulated. These differentially expressed miRNAs were found to be associated with immune/inflammatory and metabolic pathways, which are involved in vascular dysfunction. Treatment with losartan maintained the expression of the differentially expressed miRNAs, miR-31a-5p and miR-142-3p, and the levels of TNF-α, IL-1β, IL-6 and MCP-1, indicating that the differentially expressed miRNAs and their associated immune/inflammatory pathways play a pivotal role in the modulation of the vascular dysfunction in 2K1C rats. Our study provides valuable information about miRNA expression in the arteries of 2K1C rats, expanding our understanding of the complex molecular mechanisms underlying the vascular dysfunction in rats with RVH.
Manolis A, Doumas M. Sexual dysfunction: the 'prima ballerina' of hypertension-related quality-of-life complications. J Hypertens. 2008;26(11):2074-84.
Matavelli LC, Huang J, Siragy HM. Angiotensin AT₂ receptor stimulation inhibits early renal inflammation in renovascular hypertension. Hypertension. 2011;57(2):308-13.
Lerman LO, Nath KA, Rodriguez-Porcel M, Krier JD, Schwartz RS, Napoli C, Romero JC. Increased oxidative stress in experimental renovascular hypertension. Hypertension. 2001;37(2 Pt2):541-6.
Waki H, Gouraud SS, Maeda M, Raizada MK, Paton JF. Contributions of vascular inflammation in the brainstem for neurogenic hypertension. Respir Physiol Neurobiol. 2011;178(3):422-8.
Brunner HR, Kirshman JD, Sealey JE, Laragh JH. Hypertension of renal origin: evidence for two different mechanisms. Science. 1971;174(4016):1344-6.
Petrie JR, Guzik TJ, Touyz RM. Diabetes, hypertension, and cardiovascular disease: clinical insights and vascular mechanisms. Can J Cardiol. 2018;34(5):575-84.
McManus DD, Rong J, Huan T, Lacey S, Tanriverdi K, Munson PJ, Larson MG, Joehanes R, Murthy V, Shah R, Freedman JE, Levy D. Messenger RNA and microRNA transcriptomic signatures of cardiometabolic risk factors. BMC Genomics. 2017;18(1):139.
Urbich C, Kuehbacher A, Dimmeler S. Role of microRNAs in vascular diseases, inflammation, and angiogenesis. Cardiovasc Res. 2008;79(4):581-8.
Duggal B, Gupta MK, Naga Prasad SV. Potential role of microRNAs in cardiovascular disease: are they up to their hype? Curr Cardiol Rev. 2016;12(4):304-10.
Morris BJ. Renin, genes, microRNAs, and renal mechanisms involved in hypertension. Hypertension. 2015;65(5):956-62.
Sun G, Hu H, Tian X, Yue J, Yu H, Yang X, Wang Z. Identification and analysis of microRNAs in the left ventricular myocardium of two-kidney one-clip hypertensive rats. Mol Med Rep. 2013;8(2):339-44.
Lardizábal MN, Nocito AL, Daniele SM, Ornella LA, Palatnik JF, Veggi LM. Reference genes for real-time PCR quantification of microRNAs and messenger RNAs in rat models of hepatotoxicity. PLoS One. 2012;7(5):e36323.
Zarei M, Khazaei M, Sharifi MR, Pourshanazari AA. Coronary angiogenesis during experimental hypertension: is it reversible? J Res Med Sci. 2011;16(3):269-75.
Jiang L, Xue W, Wang Y. Inhibition of miR-31a-5p decreases inflammation by down-regulating IL-25 expression in human dermal fibroblast cells (CC-2511 cells) under hyperthermic stress via Wnt/β-catenin pathway. Biomed Pharmacother. 2018;107:24-33.
Calvier L, Chouvarine P, Legchenko E, Hoffmann N, Geldner J, Borchert P, Jonigk D, Mozes MM, Hansmann G. PPARγ links BMP2 and TGFβ1 pathways in vascular smooth muscle cells, regulating cell proliferation and glucose metabolism. Cell Metab. 2017;25(5):1118-34.e7.
Chan CY, Chan YC, Cheuk BL, Cheng SW. Clearance of matrix metalloproteinase-9 is dependent on low-density lipoprotein receptor-related protein-1 expression downregulated by microRNA-205 in human abdominal aortic aneurysm. J Vasc Surg. 2017;65(2):509-20.
Xia F, Sun JJ, Jiang YQ, Li CF. MicroRNA-384-3p inhibits retinal neovascularization through targeting hexokinase 2 in mice with diabetic retinopathy. J Cell Physiol. 2018;234(1):721-30.
Li Y, Xiao L, Li J, Sun P, Shang L, Zhang J, Zhao Q, Ouyang Y, Li L, Gong K. MicroRNA profiling of diabetic atherosclerosis in a rat model. Eur J Med Res. 2018;23(1):55.
Kétszeri M, Kirsch A, Frauscher B, Moschovaki-Filippidou F, Mooslechner AA, Kirsch AH, Schabhuettl C, Aringer I, Artinger K, Pregartner G, Ekart R, Breznik S, Hojs R, Goessler W, Schilcher I, Müller H, Obermayer-Pietsch B, Frank S, Rosenkranz AR, Eller P, Eller K. MicroRNA-142-3p improves vascular relaxation in uremia. Atherosclerosis. 2019;280:28-36.
Barbery CE, Celigoj FA, Turner SD, Smith RP, Kavoussi PK, Annex BH, Lysiak JJ. Alterations in microRNA expression in a murine model of diet-induced vasculogenic erectile dysfunction. J Sex Med. 2015;12(3):621-30.
Wang J, Pei Y, Zhong Y, Jiang S, Shao J, Gong J. Altered serum microRNAs as novel diagnostic biomarkers for atypical coronary artery disease. PLoS One. 2014;9(9):e107012.
Feng Y, Wang J, Yuan Y, Zhang X, Shen M, Yuan F. miR-539-5p inhibits experimental choroidal neovascularization by targeting CXCR7. FASEB J. 2018;32(3):1626-39.
Ayaz L, Dinç E. Evaluation of microRNA responses in ARPE-19 cells against the oxidative stress. Cutan Ocul Toxicol. 2018;37(2):121-6.
Hu W, Wang M, Yin H, Yao C, He Q, Yin L, Zhang C, Li W, Chang G, Wang S. MicroRNA-1298 is regulated by DNA methylation and affects vascular smooth muscle cell function by targeting connexin 43. Cardiovasc Res. 2015;107(4):534-45.
Li J, Cheng Y, Tai D, Martinka M, Welch DR, Li G. Prognostic significance of BRMS1 expression in human melanoma and its role in tumor angiogenesis. Oncogene. 2011;30(8):896-906.
Menendez-Castro C, Cordasic N, Neureiter D, Amann K, Marek I, Volkert G, Stintzing S, Jahn A, Rascher W, Hilgers KF, Hartner A. Under-expression of α8 integrin aggravates experimental atherosclerosis. J Pathol. 2015;236(1):5-16.
Bivol LM, Berge RK, Iversen BM. Tetradecylthioacetic acid prevents the inflammatory response in two-kidney, one-clip hypertension. Am J Physiol Regul Integr Comp Physiol. 2008;294(2):R438-47.
How to Cite
Copyright (c) 2020 ARCHIVES OF BIOLOGICAL SCIENCES
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Authors grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution 4.0 International License that allows others to share the work with an acknowledgment of the work’s authorship and initial publication in this journal.