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
Само за регистроване кориснике
2016
Аутори
Stanković, AleksandraKolaković, Ana
Živković, Maja
Đurić, Tamara
Bundalo, Maja M.
Končar, Igor
Davidović, Lazar
Alavantić, Dragan
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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.
Кључне речи:
Angiotensin receptor type 1 / Polymorphism / mRNA / Protein / miR-155 / Carotid plaqueИзвор:
Atherosclerosis, 2016, 248, 132-139Издавач:
- Elsevier
Финансирање / пројекти:
- Генетска основа хуманих васкуларних и инфламаторних болести (RS-175085)
- Интегрална студија идентификације регионалних генетских фактора ризика и фактора ризика животне средине за масовне незаразне болести хумане популације у Србији - INGEMA_S (RS-41028)
DOI: 10.1016/j.atherosclerosis.2016.02.032
ISSN: 0021-9150; 1879-1484
PubMed: 27016615
WoS: 000375039200017
Scopus: 2-s2.0-84962613008
Колекције
Институција/група
VinčaTY - 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 . .