The kinetics of angiotensin-I metabolism in human carotid atheroma: An emerging role for angiotensin (1-7)

Abstract

Aim: Local levels of angiotensin peptides depend on their rates of production and degradation, which induce proatherogenic or atheroprotective effects. Here, we reveal the kinetics of Angiotensin-I metabolism in paired early and advanced atherosclerotic lesions.

Methods: Lesions were spiked with labeled Ang-I* and supernatants withdrawn after 0, 10, 20, 40 and 80min. The concentration of produced Ang-II*, Ang-III*, Ang-IV* and Ang-(1-7)* peptides were measured using multiple reaction monitoring mass spectrometry coupled to ultra-performance liquid chromatography, normalized to tissue weight and initial [Ang-I*].

Results: Ang-(1-7)* was the major angiotensin peptide produced, showing increased levels in both tissue types, with 2-3 fold lower levels in advanced compared to early lesions. In contrast, Ang-II* was 2-3 fold higher in advanced compared to early lesions, showing a decrease between 0 and 40min then an increase at 80min in both tissue types. The levels of Ang-IV were stable in both tissue types across all time points. Finally, Ang-III was non-detectable in both lesions across all time points.

Conclusion: Our results suggest that progression of atherosclerosis depends on the increased levels of Ang-II along with the decreased levels of Ang-(1-7), which supports the use of Ang-(1-7) along with Angiotensin type-1 receptor (AT1R) blockers.

Keywords: Angiotensin; Atherosclerosis; Mass spectrometry; Metabolism; Renin-angiotensin-aldosterone system.