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Role of ACE I/D gene polymorphisms on the effect of ramipril in inflammatory response and myocardial injury in patients undergoing coronary artery bypass grafts
- 作者:Meral Urhan Kü?ük (1)
Nehir Sucu (2) Seyhan ?ahan Firat (3) Barlas Naim Ayta?o?lu (2) ?zden Vezir (4) Caner Bozali (2) Necmiye Canacankatan (5) Seval Kul (6) Bahar Tun?tan (3)
- 关键词:ACE gene ; ACE inhibitors ; Ramipril ; Coronary artery bypass graft (CABG)
- 刊名:European Journal of Clinical Pharmacology
- 出版年:2014
- 出版时间:December 2014
- 年:2014
- 卷:70
- 期:12
- 页码:1443-1451
- 全文大小:350 KB
- 参考文献:1. Arnett DK, Davis BR, Ford CE et al (2005) (GenHAT) study antihypertensive treatment: the genetics of hypertension-associated treatment polymorphism on blood pressure and cardiovascular risk in relation to pharmacogenetic association of the angiotensin-converting enzyme insertion/deletion. Circulation 111:3374-383 CrossRef
2. Bleumink GS, Schut AFC, Sturkenboom MCJM et al (2005) Mortality in patients with hypertension on angiotensin-I converting enzyme (ACE)-inhibitor treatment is influenced by the ACE insertion/deletion polymorphism. Pharmacogenet Genomics 15:75-1 CrossRef 3. Brasier AR, Recinos A 3rd, Eledrisi MS (2002) Vascular inflammation and the renin-angiotensin system. Arterioscler Thromb Vasc Biol 22(8):1257-266 CrossRef 4. Braunwald E, Domanski MJ, Fowler SE, Geller NL, Gersh BJ, Hsia J, Pfeffer MA, Rice MM, Rosenberg YD, Rouleau JL, Trial Investigators PEACE (2004) Angiotensin-converting-enzyme inhibition in stable coronary artery disease. N Engl J Med 351(20):2058-068 CrossRef 5. Brull DJ, Sanders J, Rumley A, Lowe GD, Humphries SE, Montgomery HE (2002) Impact of angiotensin converting enzyme inhibition on post-coronary artery bypass interleukin 6 release. Heart 87(3):252-55 CrossRef 6. Buczko W, Kramkowski K, Mogielnicki A (2006) Are the endothelial mechanisms of ACE-Is already established? Pharmacol Rep 58(Suppl):126-31 7. Burlina A, Zaninotto M, Secchiero S, Rubin D, Accorsi F (1994) Troponin T as a marker of ischemic myocardial injury. Clin Biochem 27(2):113-21 CrossRef 8. Byrne JG, Smith WJ, Murphy MP, Couper GS, Appleyard RF, Cohn LH (1992) Complete prevention of myocardial stunning, contracture, low-reflow, and edema after transplantation by blocking neutrophil adhesion molecules during reperfusion. J Thorac Cardiovasc Surg 104:1589-596 9. Cambien F, Costerousse O, Tiret L et al (1994) Plasma level and gene polymorphism of angiotensin- converting enzyme gene in relation to myocardial infarction. Circulation 90(2):669-76 CrossRef 10. Ceconi C, Francolini G, Olivares A, Comini L, Bachetti T, Ferrari R (2007) Angiotensin-converting enzyme (ACE) inhibitors have different selectivity for bradykinin binding sites of human somatic ACE. Eur J Pharmacol 577(1-):1- CrossRef 11. Celiker G, Can U, Verdi H, Yazici AC, Ozbek N, Atac FB (2009) Prevalence of thrombophilic mutations and ACE I/D polymorphism in Turkish ischemic stroke patients. Clin Appl Thromb Hemost 15(4):415-20 CrossRef 12. Ceravolo R, Maio R, Cuda G et al (2003) Relation of fasting insulin related to insertion/deletion polymorphism of angiotensin-converting enzyme-gene and cardiac mass in never-treated patients with systemic hypertension. Am J Cardiol 92(10):1234-237 CrossRef 13. Comini L, Bachetti T, Cargnoni A, Bastianon D, Gitti GL, Ceconi C, Ferrari R (2007) Therapeutic modulation of the nitric oxide: all ACE inhibitors are not equivalent. Pharmacol Res 56(1):42-8 CrossRef 14. Desideri G, Grassi D, Croce G et al. (2008) Different effects of angiotensin converting enzyme inhibitors on endothelin-1 and nitric oxide balance in human vascular endothelial cells: evidence of an oxidant-sensitive pathway. Mediators Inflamm 305087:7 15. Doi Y, Yoshizumi H, Yoshinari M et al (1996) Association between a polymorphism in the anjiotensin converting- enzyme gene and microvascular complications in Japanese patients with NIDDM. Diabetologia 39:97-02 16. Farmer JA (2000) Renin angiotensin system and ASCVD. Curr Opin Cardiol 15:141-50 - 作者单位:Meral Urhan Kü?ük (1)
Nehir Sucu (2) Seyhan ?ahan Firat (3) Barlas Naim Ayta?o?lu (2) ?zden Vezir (4) Caner Bozali (2) Necmiye Canacankatan (5) Seval Kul (6) Bahar Tun?tan (3)
1. Faculty of Medicine, Department of Medical Biology, Mustafa Kemal University, 31024, Antakya, Hatay, Turkey 2. Faculty of Medicine, Department of Cardiovascular Surgery, Mersin University, Mersin, Turkey 3. Faculty of Pharmacy, Department of Pharmacology, Mersin University, Mersin, Turkey 4. Department of Cardiovascular Surgery, Mersin Government Hospital, Mersin, Turkey 5. Faculty of Pharmacy, Department of Biochemistry, Mersin University, Mersin, Turkey 6. Faculty of Medicine, Department of Biostatistic, Gaziantep University, Gaziantep, Turkey
- ISSN:1432-1041
文摘
Background Angiotensin-converting enzyme (ACE) inhibitors block angiotensin II formation and release bradykinin, which is effective in the regulation of oxidoinflammatory injury. Some reports denote alterations in the effectiveness of ACE inhibitors in association with ACE insertion/deletion (I/D) gene polymorphisms. This study investigates the effects of ramipril on the oxidoinflammatory cytokines (IL-6, IL-8, TNF-alpha) and TnT (myocardial injury marker) and their alteration in association with ACE I/D gene polymorphisms. Methods The study group (n--1) patients received ramipril before coronary artery bypass grafting (CABG), while patients not receiving ramipril (n--1) constituted the controls. TNFα, IL-6, and IL-8 were evaluated using ELISA and TnT by electrochemiluminescence methods before the induction of anesthesia (t1), at the 20th minute following cross-clamping (t2), at the end of the operation (t3), and at the 24th hour from the commencement of anesthesia (t4). Genotyping was performed by PCR. Results Differences between the groups were significant at t4 for the TNFα and at t3 for IL-6 (p--.05). The TnT levels increased from t2 onward in the control group and were highest in t3. Changes in t3 and t4 values in both groups according to their t1 values were significant (p--.05). However, differences between the groups were insignificant (p--.05). The IL-6, IL-8, TNFα, and TnT serum levels had no correlation with the ACE I/D gene polymorphism. Conclusion Low cytokine and TnT levels in the study group, especially after cross-clamping, may indicate the protective effect of ramipril from oxidoinflammatory injury. This effect did not appear to be associated with the ACE I/D gene polymorphism.
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