Browsing by Author "Kolaković, Ana (36343835300)"

Background and Aims: 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). Conclusion: 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. © 2016 Elsevier Ireland Ltd.

Background The angiotensin II type 2 receptor (AT2R) -1332 A/G polymorphism has been denoted as functional and associated with certain cardiovascular disease phenotypes. However, there are no studies considering the association of this gene polymorphism with carotid atherosclerosis (CA) and cerebrovascular events. Therefore, the aim of our study was to investigate a possible association of the AT2R -1332 A/G polymorphism with the occurrence of carotid plaques (CPs) and history of cerebrovascular insult (CVI) in advanced CA. Methods The study group included 381 controls and 509 patients with CA consecutively admitted for endarterectomy. Genotyping was determined by polymerase chain reaction-restriction fragment length polymorphism method. The association was analyzed separately for males and females because the AT2R gene is located on the X chromosome. Results The AT2R -1332 GG genotype was associated with the advanced CA in the female study group (recessive model of inheritance, AA+AG versus GG; adjusted odds ratio [OR] = 2.25; 95% confidence interval [CI] 1.17-4.33; P =.01). In the male subgroup of patients with CA, the significant overrepresentation of G/- hemizygote was detected in patients with CVI compared to male patients without this event (crude OR = 2.05, 95% CI 1.20-3.50, P =.008). Conclusions This study suggests a gender-specific association between the AT2R -1332 A/G polymorphism and the occurrence of CP and the history of CVI in advanced CA, but further replication studies are needed. © 2016 National Stroke Association.

Introduction: The ACE I/D polymorphism was mostly investigated in association with intima-media thickness, rarely with severe atherosclerotic phenotype.Materials and methods: We investigated the association of I/D polymorphism with severe carotid atherosclerosis (CA) (stenosis > 70%) in asymptomatic and symptomatic patients undergoing carotid endarterectomy. The 504 patients subjected to endarterectomy and 492 healthy controls from a population in Serbia were investigated as a case-control study.Results: The univariate logistic regression analysis revealed ACE DD as a significant risk factor for severe CA (odds ratio [OR] = 1.3, 95% confidence interval [CI] 1.0-1.7, p = 0.04). After adjustment for the common risk factors (age, hypertension, smoking, and HDL) ACE was no longer significant. However, we found a significant independent influence of DD genotype on plaque presence in a normotensive subgroup of patients (OR 1.8, CI 1.2-3.0, p = 0.01, corrected for multiple testing). In symptomatic patients D allele carriers were significantly more frequent compared with asymptomatic patients (OR 1.6 CI 1.0-2.6, p = 0.05).Conclusions: Our data suggests that ACE I/D is not an independent risk factor for severe CA. On the other hand, a significant independent genetic influence of ACE I/D appeared in normotensive and symptomatic patients with severe CA. This should be considered in further research toward resolving the complex genetic background of severe CA phenotype. © The Author(s) 2011.

Introduction: The ACE I/D polymorphism was mostly investigated in association with intima-media thickness, rarely with severe atherosclerotic phenotype.Materials and methods: We investigated the association of I/D polymorphism with severe carotid atherosclerosis (CA) (stenosis > 70%) in asymptomatic and symptomatic patients undergoing carotid endarterectomy. The 504 patients subjected to endarterectomy and 492 healthy controls from a population in Serbia were investigated as a case-control study.Results: The univariate logistic regression analysis revealed ACE DD as a significant risk factor for severe CA (odds ratio [OR] = 1.3, 95% confidence interval [CI] 1.0-1.7, p = 0.04). After adjustment for the common risk factors (age, hypertension, smoking, and HDL) ACE was no longer significant. However, we found a significant independent influence of DD genotype on plaque presence in a normotensive subgroup of patients (OR 1.8, CI 1.2-3.0, p = 0.01, corrected for multiple testing). In symptomatic patients D allele carriers were significantly more frequent compared with asymptomatic patients (OR 1.6 CI 1.0-2.6, p = 0.05).Conclusions: Our data suggests that ACE I/D is not an independent risk factor for severe CA. On the other hand, a significant independent genetic influence of ACE I/D appeared in normotensive and symptomatic patients with severe CA. This should be considered in further research toward resolving the complex genetic background of severe CA phenotype. © The Author(s) 2011.