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 METHODS:Lesions were spiked with labeled Ang-I* and supernatants withdrawn after 0, 10, 20, 40 and 80min.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.
journal_name
Vascul Pharmacoljournal_title
Vascular pharmacologyauthors
Nehme A,Marcelo P,Nasser R,Kobeissy F,Bricca G,Zibara Kdoi
10.1016/j.vph.2016.08.001subject
Has Abstractpub_date
2016-10-01 00:00:00pages
50-56eissn
1537-1891issn
1879-3649pii
S1537-1891(16)30120-3journal_volume
85pub_type
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