Angiotensin converting enzyme (ACE) gene expression in the human left ventricle: effect of ACE gene insertion/deletion polymorphism and left ventricular function

Aims: We investigated the Effect of the angiotensin converting enzyme (ACE) I/D polymorphism and left ventricular (LV) function on ACE gene expression in tru-cut LV myocardial biopsies from 50 consecutive patients (II: 18, ID : 18, DD: 14; 40 males) with ischaemic heart disease undergoing coronary ar tery bypass grafting (CABG). Methods: The polymerase chain reaction was use d for ACE genotyping. LV function [normal (n = 22) or impaired] was determi ned by left ventriculography at cardiac catheterisation prior to bypass sur gery. ACE expression was determined (n = 46) by a competitive quantitative reverse transcription PCR assay using 5 x 10(5), 12.5 x 10(5) and 20 x 10(5 ) copies of a mutant DNA internal standard (IS). PCR products were analysed by negative film photography and laser densitometry to determine the numbe r of ACE transcripts present. Results: Mean age was similar (II: 59.1 +/- 1 0.4, ID: 57.0 +/- 10.6, DD: 61.4 +/- 6.2; P = NS) with no differences betwe en groups in sex (P = 0.25); hypertension, P = 0.31; previous myocardial in farction, P = 0.44; LV function, P = 0.23; and ACE inhibitor therapy, P = 0 .06. ACE expression per 100 ng of total RNA varied with genotype [< 5 x 10( 5) copies in II: 6, 5-12.5 x 10(5) copies in II: 6, ID: 16, DD: 4; and > 12 .5 x 10(5) (II: 4, ID: 2, DD: 8), Kendall's tau-b coefficient (tau(b))= 0.4 3, P = 0.003]. Impaired LV function also correlated with higher levels of A CE expression, Kendall's tau(b) = 0.40, P = 0.001. Conclusion: ACE gene exp ression in the left ventricle varied with ACE genotype and LV function in I HD patients undergoing CABG. (C) 2000 European Society of Cardiology. All r ights reserved.