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

Abstract

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 artery bypass grafting (CABG).

Methods:
The polymerase chain reaction was used for ACE genotyping. LV function [normal (n = 22) or impaired] was determined by left ventriculography at cardiac catheterisation prior to bypass surgery. ACE expression was determined (n = 46) by a competitive quantitative reverse transcription PCR assay using 5×105, 12.5×105 and 20×105 copies of a mutant DNA internal standard (IS). PCR products were analysed by negative film photography and laser densitometry to determine the number of ACE transcripts present.

Results:
Mean age was similar (II: 59.1±10.4, ID: 57.0±10.6, DD: 61.4±6.2; P = NS) with no differences between groups in sex (P = 0.25); hypertension, P = 0.31; previous myocardial infarction, 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 [< 5×105 copies in II: 6, 5–12.5×105 copies in II: 6, ID: 16, DD: 4; and >12.5×105 (II: 4, ID: 2, DD: 8), Kendall's tau‐b coefficient (τb) = 0.43, P = 0.003]. Impaired LV function also correlated with higher levels of ACE expression, Kendall's τb = 0.40, P = 0.001.

Conclusion:
ACE gene expression in the left ventricle varied with ACE genotype and LV function in IHD patients undergoing CABG.