COEXPRESSION 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 variati on in the level of angiotensin converting enzyme (ACE) gene expression in the right atrial appendage of patients undergoing heart surgery. D esign: The right atrial appendage was collected at the time of surgery from 30 randomly chosen patients and was rapidly frozen in liquid nit rogen prior to extraction of messenger (m)RNA. Surgical samples of hea rt valve (n = 6) and papillary muscle (n = 3) were also examined. Meth ods: Aliquots of purified mRNA were reverse-transcribed for analysis o f gene expression by a polymerase chain reaction amplification assay. Primers specific for angiotensinogen, renin, ACE, cardiac chymase, atr ial natriuretic peptide, glyceraldehyde-3-phosphate dehydrogenase, ade nosine deaminase and the transferrin receptor were used for a qualitat ive analysis of co-expression of these genes with in the same sample. In a subgroup of eight patients, a quantitative comparison of the rela tive levels of ACE gene expression was performed using a competitive p olymerase chain reaction. Results: Angiotensinogen and ACE expression were detected in all atrial, valve and ventricular samples examined, a t levels similar to those of 'housekeeping' genes such as the transfer rin receptor. Atrial renin and chymase expression were more difficult to detect, being demonstrable in only 70 and 63% of the samples, respe ctively. 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 essenti al components of the renin-angiotensin system are co-expressed at a lo w level in the right atrial appendage and are detectable in other regi ons of the human heart. Renin and chymase genes are expressed at a low er level than the angiotensinogen and ACE genes and exhibit regional d ifferences in expression. Interindividual variation in the relative le vel of ACE expression can be detected by a competitive polymerase chai n reaction.