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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
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 AT1Rs 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 LT 0.01). Conclusion: Our results indicate that the AT1R A1166C polymorphism impacts an ultrasonographicallydefined 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. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
Keywords:
Angiotensin receptor type 1 / Polymorphism / mRNA / Protein / miR-155 / Carotid plaque
TY - JOUR
AU - Stanković, Aleksandra
AU - Kolaković, Ana
AU - Živković, Maja
AU - Đurić, Tamara
AU - Bundalo, Maja M.
AU - Končar, Igor
AU - Davidović, Lazar
AU - Alavantić, Dragan
PY - 2016
UR - https://vinar.vin.bg.ac.rs/handle/123456789/1045
AB - 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 AT1Rs 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 LT 0.01). Conclusion: Our results indicate that the AT1R A1166C polymorphism impacts an ultrasonographicallydefined 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. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
PB - Elsevier
T2 - Atherosclerosis
T1 - 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
VL - 248
SP - 132
EP - 139
DO - 10.1016/j.atherosclerosis.2016.02.032
ER -
@article{
author = "Stanković, Aleksandra and Kolaković, Ana and Živković, Maja and Đurić, Tamara and Bundalo, Maja M. and Končar, Igor and Davidović, Lazar and Alavantić, Dragan",
year = "2016",
abstract = "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 AT1Rs 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 LT 0.01). Conclusion: Our results indicate that the AT1R A1166C polymorphism impacts an ultrasonographicallydefined 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. (C) 2016 Elsevier Ireland Ltd. All rights reserved.",
publisher = "Elsevier",
journal = "Atherosclerosis",
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",
volume = "248",
pages = "132-139",
doi = "10.1016/j.atherosclerosis.2016.02.032"
}
Stanković, A., Kolaković, A., Živković, M., Đurić, T., Bundalo, M. M., Končar, I., Davidović, L.,& Alavantić, D.. (2016). 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. in Atherosclerosis
Elsevier., 248, 132-139.
https://doi.org/10.1016/j.atherosclerosis.2016.02.032
Stanković A, Kolaković A, Živković M, Đurić T, Bundalo MM, Končar I, Davidović L, Alavantić D. 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. in Atherosclerosis. 2016;248:132-139.
doi:10.1016/j.atherosclerosis.2016.02.032 .
Stanković, Aleksandra, Kolaković, Ana, Živković, Maja, Đurić, Tamara, Bundalo, Maja M., Končar, Igor, Davidović, Lazar, Alavantić, Dragan, "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" in Atherosclerosis, 248 (2016):132-139,
https://doi.org/10.1016/j.atherosclerosis.2016.02.032 . .
