G K Davis1, R W Millner, D H Roberts. 1. Regional Cardiothoracic Centre, Victoria Hospital, Blackpool, UK. gershan@hotmail.com
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 5x10(5), 12. 5x10(5) and 20x10(5) 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 [<5x10(5) copies in II: 6, 5-12.5x10(5) copies in II: 6, ID: 16, DD: 4; and >12.5x10(5) (II: 4, ID: 2, DD: 8), Kendall's tau-b coefficient (tau(b))=0.43, P=0.003]. Impaired LV function also correlated with higher levels of ACE expression, Kendall's tau(b)=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.
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 5x10(5), 12. 5x10(5) and 20x10(5) 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 [<5x10(5) copies in II: 6, 5-12.5x10(5) copies in II: 6, ID: 16, DD: 4; and >12.5x10(5) (II: 4, ID: 2, DD: 8), Kendall's tau-b coefficient (tau(b))=0.43, P=0.003]. Impaired LV function also correlated with higher levels of ACE expression, Kendall's tau(b)=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.