title: Expression of angiotensin-converting enzyme 2 and its end product angiotensin 1-7 is increased in diabetic atheroma: implications for inflammation and neovascularization.
abstract: OBJECTIVE
  The angiotensin-converting enzyme 2 (ACE2) and its end product angiotensin 1-7 (Ang1-7) are key counterregulatory proteins to offset the deleterious effects of angiotensin II. ACE2 is decreased in diabetic kidney disease but overexpressed in metabolically active atheroma. We tested the hypothesis that ACE2 is increased in diabetic peripheral atheroma, concomitantly with Ang1-7, angiotensin II receptor 1 (AT1R), proinflammatory cytokines, macrophage infiltration, and plaque neovascularization.
  
  
  RESULTS
  Peripheral atherectomy plaques collected from 12 diabetic (DM) and 12 non-DM patients were immunostained for ACE2, Ang1-7, AT1R, and proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Macrophage infiltration and neovascularization were counted using double-label immunochemistry with CD68/CD3 and CD34, respectively. Quantification was performed blindly by randomly counting positively stained cells in 20 high-power fields using previously validated methods. Tissue content of ACE2, Ang1-7, and AT1R was increased in DM when compared to non-DM (P<.0001). IL-6 and TNF-α were also increased in DM when compared to non-DM (P<.0001), as well as macrophage infiltration score and neovessel counting (P<.0001).
  
  
  CONCLUSIONS
  Expression of ACE2 and its end product Ang1-7 is increased in DM atheroma, along with overexpression of AT1R, IL6, TNF-α, macrophage infiltration, and neovascularization. These results suggest that the renin-angiotensin system counterregulatory pathway may be preserved in metabolically active atheroma, offering potential targets for future therapies in diabetic atherosclerosis.
authors: The Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai School of Medicine, New York, NY, USA.
authors: K-Raman
authors: KR
authors: Purushothaman
authors: Prakash
authors: P
authors: Krishnan
authors: Meerarani
authors: M
authors: Purushothaman
authors: Jose
authors: J
authors: Wiley
authors: Carlos L
authors: CL
authors: Alviar
authors: Fernando J
authors: FJ
authors: Ruiz
authors: Yelena
authors: Y
authors: Zubatov
authors: Annapoorna S
authors: AS
authors: Kini
authors: Samin K
authors: SK
authors: Sharma
authors: Valentin
authors: V
authors: Fuster
authors: Pedro R
authors: PR
authors: Moreno
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000803:Angiotensin I / Q000032:analysis*; D000085962:Angiotensin-Converting Enzyme 2; D050197:Atherosclerosis / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003925:Diabetic Angiopathies / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D018836:Inflammation Mediators / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D008264:Macrophages / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D010446:Peptide Fragments / Q000032:analysis*; D007703:Peptidyl-Dipeptidase A / Q000032:analysis*; D058226:Plaque, Atherosclerotic; D044140:Receptor, Angiotensin, Type 1 / Q000032:analysis; D012084:Renin-Angiotensin System; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D015854:Up-Regulation
chemical_list: C544065:AGTR1 protein, human; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D010446:Peptide Fragments; D044140:Receptor, Angiotensin, Type 1; D014409:Tumor Necrosis Factor-alpha; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2; C118790:angiotensin I (1-7)