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Effects of ACE inhibition on circulating endothelial progenitor cells, vascular damage, and oxidative stress in hypertensive patients

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Abstract

Purpose

The pathogenic role of angiotensin-converting enzyme (ACE) inhibition in hypertensive patients regarding endothelial progenitor-cell (EPC) function is still poorly understood. The aim of the study was to evaluate EPC number, function, and relationship to carotid intima media thickness (IMT) progression.

Methods

We studied 36 newly diagnosed mildly hypertensive patients free of cardiovascular disease and related risk factors without prior or concurrent therapy with ACE inhibitors. Patients were randomized to receive enalapril 20 mg/day (n = 18) or zofenopril 30 mg/day (n = 18). EPC number and migrating capacity, plasma nitrite and nitrate (NOx), and isoprostane concentrations were evaluated. Carotid IMT was determined by ultrasonography at baseline and after 1 and 5 years of follow-up.

Results

EPC number increased during the follow-up, with no statistical differences between treatment groups. There was an inverse correlation between circulating EPCs and IMT increase over time. Plasma NOx decreased during the study without evident differences between treatment groups. Isoprostanes decreased more markedly in zofenopril-treated patients. Multiple linear regression model demonstrated that carotid IMT was significantly inversely correlated with EPC but not with migratory cells after adjusting for confounders.

Conclusions

The study demonstrated that EPC levels increased during the follow-up in both groups of newly diagnosed hypertensive patients treated with ACE inhibitors. These drugs prevented progression of vascular damage, with an inverse correlation between circulating EPC levels and IMT values.

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Acknowledgments

This work was supported in part by grants from the Progetto di Rilevante Interesse Nazionale Ministero Italiano Università e Ricerca 2006 [Code 0622153_002 “Meccanismi fisiopatologici di danno vascolare/trombotico ed angiogenesi” (to CN), Ricerca Finalizzata del Ministero della Salute 2007 (to FC), and the Fondation Jerome Lejeune, France (to CN)

Author contributions

Dr. Cacciatore, Dr. Vitale, and Prof. Napoli played a major role in the writing of the manuscript. Dr. Cacciatore and Dr. Vitale were also responsible for statistical analysis. Dr. Liguori, and Dr. Bruzzese had the overall responsibility for all in-hospital activities, in particular, coordination of the clinical team, permissions to access medical records, obtaining informed consent, and clinical protocols. Dr. de Nigris, Dr. Fiorito, Dr. Infante, and Dr. Minucci provided execution and interpretation of clinical laboratory measurements. Prof. Napoli and Prof. Ignarro were involved in the first series of studies addressing the vascular effects of ACE inhibitors, thus providing the rationale and aim of the study. However, strong support on the detailed design of the study and its follow-up was given by Prof. Donatelli, Dr. Liguori, and Dr. Cacciatore.

Conflict of Interest

None of the authors have a conflict of interest in connection with this study

Author information

Authors and Affiliations

  1. Cardiovascular Rehabilitation, Salvatore Maugeri Foundation, IRCCS, Institute of Telese, 82037, Benevento, Italy

    Francesco Cacciatore & Dino Franco Vitale

  2. Division of Cardiology-UTIC, Ospedale Pellegrini, ASL NA1, 80100, Naples, Italy

    Giuseppe Bruzzese & Antonio Liguori

  3. Department of General Pathology, Excellence Research Centre on Cardiovascular Diseases, Immunohematology and Transplantation Centre, 1st School of Medicine, II University of Naples, 80138, Naples, Italy

    Filomena de Nigris, Carmela Fiorito, Teresa Infante, Pellegrino Biagio Minucci & Claudio Napoli

  4. Cardiosurgery Department, University of Milan, 20142, Milan, Italy

    Francesco Donatelli

  5. Fondazione SDN, IRCCS, 80131, Naples, Italy

    Teresa Infante & Claudio Napoli

  6. Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA

    Louis Joseph Ignarro

Authors
  1. Francesco Cacciatore
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  2. Giuseppe Bruzzese
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  3. Dino Franco Vitale
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  4. Antonio Liguori
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  5. Filomena de Nigris
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  7. Teresa Infante
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  8. Francesco Donatelli
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  9. Pellegrino Biagio Minucci
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  11. Claudio Napoli
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Corresponding author

Correspondence to Francesco Cacciatore.

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Cacciatore, F., Bruzzese, G., Vitale, D.F. et al. Effects of ACE inhibition on circulating endothelial progenitor cells, vascular damage, and oxidative stress in hypertensive patients. Eur J Clin Pharmacol 67, 877–883 (2011). https://doi.org/10.1007/s00228-011-1029-0

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  • DOI: https://doi.org/10.1007/s00228-011-1029-0

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