Novel role of aminopeptidase-A in angiotensin-(1-7) metabolism post myocardial infarction

Title

Novel role of aminopeptidase-A in angiotensin-(1-7) metabolism post myocardial infarction

Creator

Alghamri M S; Morris M; Meszaros J G; Elased K M; Grobe N

Publisher

American Journal of Physiology-Heart and Circulatory Physiology

Date

2014
2014-04

Description

Aminopeptidase-A (APA) is a less well-studied enzyme of the renin-angiotensin system. We propose that it is involved in cardiac angiotensin (ANG) metabolism and its pathologies. ANG-(1-7) can ameliorate remodeling after myocardial injury. The aims of this study are to 1) develop mass spectrometric (MS) approaches for the assessment of ANG processing by APA within the myocardium; and 2) investigate the role of APA in cardiac ANG-(1-7) metabolism after myocardial infarction (MI) using sensitive MS techniques. MI was induced in C57Bl/6 male mice by ligating the left anterior descending (LAD) artery. Frozen mouse heart sections (in situ assay) or myocardial homogenates (in vitro assay) were incubated with the endogenous APA substrate, ANG II. Results showed concentration-and time-dependent cardiac formation of ANG III from ANG II, which was inhibited by the specific APA inhibitor, 4-amino-4-phosphonobutyric acid. Myocardial APA activity was significantly increased 24 h after LAD ligation (0.82 +/- 0.02 vs. 0.32 +/- 0.02 rho mol.min(-1).mu g(-1), MI vs. sham, P < 0.01). Both MS enzyme assays identified the presence of a new peptide, ANG-(2-7), m/z 784, which accumulated in the MI (146.45 +/- 6.4 vs. 72.96 +/- 7.0%, MI vs. sham, P < 0.05). Use of recombinant APA enzyme revealed that APA is responsible for ANG-(2-7) formation from ANG-(1-7). APA exhibited similar substrate affinity for ANG-(1-7) compared with ANG II {K-m (ANG II) = 14.67 +/- 1.6 vs. K-m [ANG-(1-7)] = 6.07 +/- 1.12 mu mol/l, P < 0.05}. Results demonstrate a novel role of APA in ANG-(1-7) metabolism and suggest that the upregulation of APA, which occurs after MI, may deprive the heart of cardioprotective ANG-(1-7). Thus APA may serve as a potentially novel therapeutic target for management of tissue remodeling after MI.

Subject

ace2; Aminopeptidase A; angiotensin peptides; antihypertensive agents; carboxypeptidase; Cardiovascular System & Cardiology; enzyme; inhibitors; kidney; MALDI-imaging; mass-spectrometry; Myocardial infarction; Physiology; renal damage; renin-angiotensin system; spontaneously hypertensive-rats; system

Format

Journal Article or Conference Abstract Publication

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Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

H1032-H1040

Issue

7

Volume

306

Citation

Alghamri M S; Morris M; Meszaros J G; Elased K M; Grobe N, “Novel role of aminopeptidase-A in angiotensin-(1-7) metabolism post myocardial infarction,” NEOMED Bibliography Database, accessed September 17, 2021, https://neomed.omeka.net/items/show/8461.

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