title: Angiotensin receptor type 1 polymorphism A1166C is associated with altered AT1R and miR-155 expression in carotid plaque tissue and development of hypoechoic carotid plaques.
abstract: OBJECTIVE
  The principal biologic effects of the renin-angiotensin system are mediated by activation of the AT1R receptor. The microRNA miR-155 regulates AT1R expression, with both its, and AT1R's activity, linked to atherosclerosis. Target sites for miR-155 lie within the 3' UTR of the human AT1R gene, and include the AT1R A1166C polymorphism. Thus far, only levels of circulating miR-155 have been investigated with respect to A1166C genotypes. We hypothesized that the A1166C polymorphism could correlate with different, ultra-sonographically defined plaque phenotypes, as well as with an altered expression of AT1R mRNA and protein in human carotid plaques (CP), and altered expression of miR-155 in patients with advanced atherosclerosis.
  
  
  METHODS
  Our study cohort comprised 411 patients with advanced carotid atherosclerosis (298 hyperechoic; 113 hypoechoic plaques). PCR analyses identified A1166C genotypes; quantitative real-time PCR determined AT1R and miR-155 expression levels, with AT1R protein expression evaluated by western blot.
  
  
  RESULTS
  Genotypes containing the C allele bore a significant association with the hypoechoic plaque phenotype (adjusted OR 1.87, 95% CI 1.16-3.00, p = 0.01). The expression of AT1R mRNA and miR-155 were significantly up-regulated in the CPs of CC genotype carriers compared to the AA/AC genotypes (p = 0.032, p = 0.015, respectively). AT1R protein expression was also significantly higher for CC genotypes (p < 0.01).
  
  
  CONCLUSIONS
  Our results indicate that the AT1R A1166C polymorphism impacts an ultrasonographically-defined human plaque phenotype, with intra-plaque AT1R and miR-155 expression altered in advanced carotid atherosclerosis. Validation and replication of these data should contribute to an improved personalized therapy with which to prevent carotid atherosclerosis.
authors.affiliation: Vinča Institute of Nuclear Sciences, Laboratory for Radiobiology and Molecular Genetics, University of Belgrade, Belgrade, Serbia. Electronic address: alexas@vinca.rs.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Stanković
authors.affiliation: Vinča Institute of Nuclear Sciences, Laboratory for Radiobiology and Molecular Genetics, University of Belgrade, Belgrade, Serbia.
authors.forename: Ana
authors.initials: A
authors.lastname: Kolaković
authors.affiliation: Vinča Institute of Nuclear Sciences, Laboratory for Radiobiology and Molecular Genetics, University of Belgrade, Belgrade, Serbia.
authors.forename: Maja
authors.initials: M
authors.lastname: Živković
authors.affiliation: Vinča Institute of Nuclear Sciences, Laboratory for Radiobiology and Molecular Genetics, University of Belgrade, Belgrade, Serbia.
authors.forename: Tamara
authors.initials: T
authors.lastname: Djurić
authors.affiliation: Vinča Institute of Nuclear Sciences, Laboratory for Radiobiology and Molecular Genetics, University of Belgrade, Belgrade, Serbia.
authors.forename: Maja
authors.initials: M
authors.lastname: Bundalo
authors.affiliation: Clinic for the Vascular and Endovascular Surgery, Clinical Centre of Serbia, Belgrade, Serbia; Medical Faculty, University of Belgrade, Belgrade, Serbia.
authors.forename: Igor
authors.initials: I
authors.lastname: Končar
authors.affiliation: Clinic for the Vascular and Endovascular Surgery, Clinical Centre of Serbia, Belgrade, Serbia; Medical Faculty, University of Belgrade, Belgrade, Serbia.
authors.forename: Lazar
authors.initials: L
authors.lastname: Davidović
authors.affiliation: Vinča Institute of Nuclear Sciences, Laboratory for Radiobiology and Molecular Genetics, University of Belgrade, Belgrade, Serbia.
authors.forename: Dragan
authors.initials: D
authors.lastname: Alavantić
mesh_terms: D000483:Alleles; D050197:Atherosclerosis / Q000235:genetics*; D002339:Carotid Arteries / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D010641:Phenotype; D058226:Plaque, Atherosclerotic / Q000235:genetics*; D011110:Polymorphism, Genetic; D060888:Real-Time Polymerase Chain Reaction; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics*
chemical_list: C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D044140:Receptor, Angiotensin, Type 1
keywords: Angiotensin receptor type 1; Carotid plaque; Polymorphism; Protein; mRNA; miR-155