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ACE2 gene expression is up-regulated in the human failing heart.

Goulter AB, Goddard MJ, Allen JC, Clark KL - BMC Med (2004)

Bottom Line: ACE2 is a novel homologue of angiotensin converting enzyme (ACE).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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Pharmagene Laboratories, 2 Orchard Road, Royston, Hertfordshire, UK, SG8 5HD. andrew.goulter@pharmagene.com

ABSTRACT

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.

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Quantitative expression profile of ACE2; ACE; ANF and AT1 in control; IDC and ICM human left ventricular myocardium. ACE2; ACE; ANF and AT1 mRNA copy number in human left ventricular myocardium classified as Control (non-diseased) (n = 9); IDC-idiopathic dilated cardiomyopathy (n = 11); ICM-ischemic cardiomyopathy (n = 12). Corresponding levels of the housekeeping gene GAPDH are also shown. Each bar represents the geometric mean mRNA copy number with 95 % CI on a log scale. * – P < 0.05 Vs. Control.
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Figure 1: Quantitative expression profile of ACE2; ACE; ANF and AT1 in control; IDC and ICM human left ventricular myocardium. ACE2; ACE; ANF and AT1 mRNA copy number in human left ventricular myocardium classified as Control (non-diseased) (n = 9); IDC-idiopathic dilated cardiomyopathy (n = 11); ICM-ischemic cardiomyopathy (n = 12). Corresponding levels of the housekeeping gene GAPDH are also shown. Each bar represents the geometric mean mRNA copy number with 95 % CI on a log scale. * – P < 0.05 Vs. Control.

Mentions: Atrial natriuretic factor (ANF) mRNA was evaluated as a positive control and was confirmed to be up-regulated by approximately 13 and 8-fold in IDC and ICM, respectively, versus the control group (see Table 3; Figure 1). Also in accordance with previous reports, relative to non-diseased ventricle, ACE mRNA was increased approximately 3-fold and 2-fold in IDC and ICM, respectively. ACE2 mRNA was expressed in non-diseased ventricle (see Table 3, Figure 1) and expression was further enhanced in IDC (~2 fold increase) and ICM (~2-fold increase). Expression of the angiotensin AT1 receptor mRNA was not changed in either of the heart failure groups relative to control. Renin mRNA was not present (zero copies) in ventricle from either of the groups. The renin primer probe set was validated by demonstrating expression of renin mRNA (mean copy number = 1158) in human renal cortex from three donors.


ACE2 gene expression is up-regulated in the human failing heart.

Goulter AB, Goddard MJ, Allen JC, Clark KL - BMC Med (2004)

Quantitative expression profile of ACE2; ACE; ANF and AT1 in control; IDC and ICM human left ventricular myocardium. ACE2; ACE; ANF and AT1 mRNA copy number in human left ventricular myocardium classified as Control (non-diseased) (n = 9); IDC-idiopathic dilated cardiomyopathy (n = 11); ICM-ischemic cardiomyopathy (n = 12). Corresponding levels of the housekeeping gene GAPDH are also shown. Each bar represents the geometric mean mRNA copy number with 95 % CI on a log scale. * – P < 0.05 Vs. Control.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC425604&req=5

Figure 1: Quantitative expression profile of ACE2; ACE; ANF and AT1 in control; IDC and ICM human left ventricular myocardium. ACE2; ACE; ANF and AT1 mRNA copy number in human left ventricular myocardium classified as Control (non-diseased) (n = 9); IDC-idiopathic dilated cardiomyopathy (n = 11); ICM-ischemic cardiomyopathy (n = 12). Corresponding levels of the housekeeping gene GAPDH are also shown. Each bar represents the geometric mean mRNA copy number with 95 % CI on a log scale. * – P < 0.05 Vs. Control.
Mentions: Atrial natriuretic factor (ANF) mRNA was evaluated as a positive control and was confirmed to be up-regulated by approximately 13 and 8-fold in IDC and ICM, respectively, versus the control group (see Table 3; Figure 1). Also in accordance with previous reports, relative to non-diseased ventricle, ACE mRNA was increased approximately 3-fold and 2-fold in IDC and ICM, respectively. ACE2 mRNA was expressed in non-diseased ventricle (see Table 3, Figure 1) and expression was further enhanced in IDC (~2 fold increase) and ICM (~2-fold increase). Expression of the angiotensin AT1 receptor mRNA was not changed in either of the heart failure groups relative to control. Renin mRNA was not present (zero copies) in ventricle from either of the groups. The renin primer probe set was validated by demonstrating expression of renin mRNA (mean copy number = 1158) in human renal cortex from three donors.

Bottom Line: ACE2 is a novel homologue of angiotensin converting enzyme (ACE).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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Pharmagene Laboratories, 2 Orchard Road, Royston, Hertfordshire, UK, SG8 5HD. andrew.goulter@pharmagene.com

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus