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

• Published in: European journal of clinical pharmacology Vol. 70; no. 12; pp. 1443 - 1451
• Main Authors: Urhan Küçük, Meral, Sucu, Nehir, Şahan Firat, Seyhan, Aytaçoğlu, Barlas Naim, Vezir, Özden, Bozali, Caner, Canacankatan, Necmiye, Kul, Seval, Tunçtan, Bahar
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.12.2014; Springer; Springer Nature B.V
• Subjects: ACE inhibitors; Aged; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cardiology. Vascular system; Cardiotonic Agents - pharmacology; Coronary Artery Bypass; Coronary heart disease; Female; Genotype & phenotype; Heart; Heart Injuries - blood; Heart surgery; Humans; Interleukin-6 - blood; Interleukin-8 - blood; Male; Medical sciences; Myocarditis. Cardiomyopathies; Peptidyl-Dipeptidase A - genetics; Pharmacogenetics; Pharmacology; Pharmacology. Drug treatments; Pharmacology/Toxicology; Polymorphism; Polymorphism, Genetic; Ramipril - pharmacology; Troponin T - blood; Tumor Necrosis Factor-alpha - blood; Coronary artery bypass graft (CABG); Ramipril; ACE gene; ACE inhibitors; Human; Genetic variability; Enzyme; Enzyme inhibitor; Cardiovascular disease; Genotype; Inflammation; Coronary heart disease; Myocardial disease; D gene; Peptidases; Coronary artery bypass; Peptidyl-dipeptidase A; Hydrolases; Peptidyl-dipeptidases; Antihypertensive agent; Graft; Genetics; ACE inhibitor
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/s00228-014-1751-5

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  = 51) patients received ramipril before coronary artery bypass grafting (CABG), while patients not receiving ramipril ( n  = 51) 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  < 0.05). 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  < 0.05). However, differences between the groups were insignificant ( p  > 0.05). 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.