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Co-expression of renin-angiotensin system component genes in human atrial tissue
Objectives:
To detect co-expression of genes coding for components of the renin-angiotensin system and investigate the potential for variation in the level of angiotensin converting enzyme (ACE) gene expression in the right atrial appendage of patients undergoing heart surgery.
Design:
The right atrial appendage was collected at the time of surgery from 30 randomly chosen patients and was rapidly frozen in liquid nitrogen prior to extraction of messenger (m)RNA. Surgical samples of heart valve (n = 6) and papillary muscle (n = 3) were also examined.
Methods:
Aliquots of purified mRNA were reverse-transcribed for analysis of gene expression by a polymerase chain reaction amplification assay. Primers specific for angiotensinogen, renin, ACE, cardiac chymase, atrial natriuretic peptide, glyceraldehyde-3-phosphate dehydrogenase, adenosine deaminase and the transferrin receptor were used for a qualitative analysis of co-expression of these genes within the same sample. In a subgroup of eight patients, a quantitative comparison of the relative levels of ACE gene expression was performed using a competitive polymerase chain reaction.
Results:
Angiotensinogen and ACE expression were detected in all atrial, valve and ventricular samples examined, at levels similar to those of 'housekeeping' genes such as the transferrin receptor. Atrial renin and chymase expression were more difficult to detect, being demonstrable in only 70 and 63% of the samples, respectively. Higher levels of chymase were detected in ventricular samples than in atrial tissues. A quantitative analysis of ACE expression in eight atrial samples provided evidence of interindividual variation in the relative level of atrial ACE expression.
Conclusions:
The essential components of the renin-angiotensin system are co-expressed at a low level in the right atrial appendage and are detectable in other regions of the human heart. Renin and chymase genes are expressed at a lower level than the angiotensinogen and ACE genes and exhibit regional differences in expression. Interindividual variation in the relative level of ACE expression can be detected by a competitive polymerase chain reaction.