Expression of angiotensin-converting enzyme 2 and its end product angiotensin 1-7 is increased in diabetic atheroma: Implications for inflammation and neovascularization

K. Raman Purushothaman, Prakash Krishnan, Meerarani Purushothaman, Jose Wiley, Carlos L. Alviar, Fernando J. Ruiz, Yelena Zubatov, Annapoorna S. Kini, Samin K. Sharma, Valentin Fuster, Pedro R. Moreno

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Aims: 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. Methods and 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). Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)42-48
Number of pages7
JournalCardiovascular Pathology
Volume22
Issue number1
DOIs
StatePublished - Jan 2013
Externally publishedYes

Keywords

  • ACE2
  • Diabetes mellitus
  • Inflammation
  • Neovascularization
  • Peripheral vascular disease

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Cardiology and Cardiovascular Medicine

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