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

Abstract

AimLocal 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. MethodsLesions were spiked with labeled Ang-I* and supernatants withdrawn after 0, 10, 20, 40 and 80min.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*]. ResultsAng-(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. ConclusionOur 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.