title: The kinetics of angiotensin-I metabolism in human carotid atheroma: An emerging role for angiotensin (1-7).
abstract: 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.
  
  
  
  Lesions were spiked with labeled Ang-I* and supernatants withdrawn after 0, 10, 20, 40 and 80min.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*].
  
  
  
  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.
  
  
  
  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.
authors: ER045, Laboratory of stem cells, DSST, Lebanese University, Beirut, Lebanon; EA4173, Functional genomics of arterial hypertension, UCBL-1, Lyon, France.
authors: Ali
authors: A
authors: Nehme
authors: ICAP Facility - Health and Research University Center, University of Amiens, France.
authors: Paulo
authors: P
authors: Marcelo
authors: ER045, Laboratory of stem cells, DSST, Lebanese University, Beirut, Lebanon; Department of Biology, Faculty of Sciences-I, Lebanese University, Beirut, Lebanon.
authors: Roudaina
authors: R
authors: Nasser
authors: Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
authors: Firas
authors: F
authors: Kobeissy
authors: ER045, Laboratory of stem cells, DSST, Lebanese University, Beirut, Lebanon.
authors: Giampiero
authors: G
authors: Bricca
authors: ER045, Laboratory of stem cells, DSST, Lebanese University, Beirut, Lebanon; Department of Biology, Faculty of Sciences-I, Lebanese University, Beirut, Lebanon. Electronic address: kzibara@ul.edu.lb.
authors: Kazem
authors: K
authors: Zibara
mesh_terms: D000803:Angiotensin I / Q000378:metabolism*; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000378:metabolism; D000805:Angiotensin III / Q000378:metabolism; D002340:Carotid Artery Diseases / Q000378:metabolism* / Q000473:pathology; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D018450:Disease Progression; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D010446:Peptide Fragments / Q000378:metabolism*; D058226:Plaque, Atherosclerotic / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors
chemical_list: D010446:Peptide Fragments; D000804:Angiotensin II; D000805:Angiotensin III; C012877:angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-; D000803:Angiotensin I; C118790:angiotensin I (1-7)
keywords: Angiotensin; Atherosclerosis; Mass spectrometry; Metabolism; Renin-angiotensin-aldosterone system