MicroRNA-22 and promoter motif polymorphisms at the Chga locus in genetic hypertension: functional and therapeutic implications for gene expression and the pathogenesis of hypertension

0395602 - FGÚ 2014 RIV GB eng J - Journal Article
Friese, R. S. - Altshuler, A. E. - Zhang, K. - Miramontes-Gonzales, J. P. - Hightower, C. M. - Jirout, M. L. - Salem, R. M. - Gayen, J. R. - Mahapatra, N. R. - Biswas, N. - Cale, M. - Vaingankar, S. M. - Kim, H.-S. - Courel, M. - Taupenot, L. - Ziegler, M. G. - Schork, N. J. - Pravenec, Michal - Mahata, S. K. - Schmid-Schönbein, G. W. - O´Connor, D. T.
MicroRNA-22 and promoter motif polymorphisms at the Chga locus in genetic hypertension: functional and therapeutic implications for gene expression and the pathogenesis of hypertension.
Human Molecular Genetics. Roč. 22, č. 18 (2013), s. 3624-3640. ISSN 0964-6906. E-ISSN 1460-2083
R&D Projects: GA ČR(CZ) GAP301/10/0290; GA ČR(CZ) GAP301/12/0696
Institutional support: RVO:67985823
Keywords : Chromogranin A * spontaneously hypertensive rat * mir-22 * blood pressure * catecholamines
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 6.677, year: 2013

Using HXB/BXH recombinant inbred strain linkage and correlations, we demonstrated genetic determination of Chga (Chromogranin A) expression in spontaneously hypertensive rat (SHR), including a cis-quantitative trait loci (QTLs) (i.e. at the Chga locus), and such expression influenced biochemical determinants of blood pressure, including a cascade of catecholamine biosynthetic enzymes, catecholamines themselves and steroids. Luciferase reporter assays demonstrated that the 3′-UTR polymorphism (which disrupts a microRNA miR-22 motif) and promoter polymorphisms altered gene expression consistent with the decline in SHR central Chga expression. Accordingly, we demonstrated that in vivo administration of miR-22 antagomir to SHR causes substantial (18 mmHg) reductions in blood pressure, opening a novel therapeutic avenue for hypertension
Permanent Link: http://hdl.handle.net/11104/0223591