ACE2 gene expression is up-regulated in the human failing heart.
BACKGROUND
ACE2 is a novel homologue of angiotensin converting enzyme (ACE). ACE2 is highly expressed in human heart and animal data suggest that ACE2 is an essential regulator of cardiac function in vivo. Since overactivity of the renin-angiotensin system contributes to the progression of heart failure, this investigation assessed changes in gene expression of ACE2, ACE, AT1 receptor and renin in the human failing heart.


METHODS
The sensitive technique of quantitative reverse transcriptase polymerase chain reaction was used to determine the level of mRNA expression of ACE and ACE2 in human ventricular myocardium from donors with non-diseased hearts (n = 9), idiopathic dilated cardiomyopathy (IDC, n = 11) and ischemic cardiomyopathy (ICM, n = 12). Following logarithmic transformation of the data, a one-way analysis of variance was performed for each target gene followed by a Dunnett's test to compare the two disease groups IDC and ICM versus control.


RESULTS
As anticipated, ACE mRNA was found to be significantly increased in the failing heart with a 3.1 and 2.4-fold up-regulation found in IDC and ICM relative to non-diseased myocardium. Expression of ACE2 mRNA was also significantly up-regulated in IDC (2.4-fold increase) and ICM (1.8-fold increase) versus non-diseased myocardium. No change in angiotensin AT1 receptor mRNA expression was found in failing myocardium and renin mRNA was not detected.


CONCLUSIONS
These data suggest that ACE2 is up-regulated in human IDC and ICM and are consistent with the hypothesis that differential regulation of this enzyme may have important functional consequences in heart failure. This strengthens the hypothesis that ACE2 may be a relevant target for the treatment of heart failure and will hopefully spur further studies to clarify the functional effects in human myocardium of ACE2 derived peptides.
Goulter
Andrew B
AB
Pharmagene Laboratories, 2 Orchard Road, Royston, Hertfordshire, UK, SG8 5HD. andrew.goulter@pharmagene.com
Goddard
Martin J
MJ
Allen
Jennifer C
JC
Clark
Kenneth L
KL
D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000085962:Angiotensin-Converting Enzyme 2; D002268:Carboxypeptidases / Q000235:genetics*; D002311:Cardiomyopathy, Dilated / Q000201:enzymology*; D002675:Child, Preschool; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000201:enzymology*; D009206:Myocardium / Q000201:enzymology*; D007703:Peptidyl-Dipeptidase A; D015854:Up-Regulation
D002268:Carboxypeptidases; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2