title: Effect of a stable Angiotensin-(1-7) analogue on progenitor cell recruitment and cardiovascular function post myocardial infarction.
abstract: BACKGROUND
  Angiotensin-(1-7) improves cardiac function and remodeling after myocardial infarction (MI). This may involve recruitment of hematopoietic progenitor cells that support angiogenesis. However, angiotensin-(1-7) is rapidly metabolized in plasma and tissue. The authors investigated in mice the effect of a metabolically stable angiotensin-(1-7) analogue, cyclic angiotensin-(1-7), on progenitor cell recruitment and on the heart post MI, when given in the angiogenesis phase of remodeling.
  
  
  RESULTS
  Angiogenic progenitor cell recruitment was measured by using flow cytometry 24 and 72 hours after a daily bolus injection of cyclic angiotensin-(1-7) in healthy C57BL/6 mice. Further, mice underwent MI or sham surgery and subsequently received saline or 2 different doses of cyclic angiotensin-(1-7) for 3 or 9 weeks. Cyclic angiotensin-(1-7) increased circulating hematopoietic progenitor cells at 24 hours but not 72 hours. Post MI, cyclic angiotensin-(1-7) diminished cardiomyocyte hypertrophy and reduced myogenic tone, without altering cardiovascular function or cardiac histology at 9 weeks. Importantly, cyclic angiotensin-(1-7)-treated mice had reduced cardiac capillary density at 3 weeks after MI but not after 9 weeks. Finally, cyclic angiotensin-(1-7) decreased tube formation by cultured human umbilical vein endothelial cells.
  
  
  CONCLUSIONS
  Our results suggest that cyclic angiotensin-(1-7), when given early after MI, recruits progenitor cells but does not lead to improved angiogenesis, most likely because it simultaneously exerts antiangiogenic effect in adult endothelial cells. Apparently, optimal treatment with cyclic angiotensin-(1-7) depends on the time point of onset of application after MI.
authors: Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus MC, Erasmus University Medical Center, Rotterdam, The Netherlands (B.S.P., R.V.V., R.D.V., J.D., A.M.R.).
authors: Bruno
authors: B
authors: Sevá Pessôa
authors: Department of General and Interventional Cardiology, University Heart Center Hamburg Eppendorf, Germany (P.M.B., D.W.).
authors: Peter Moritz
authors: PM
authors: Becher
authors: Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus MC, Erasmus University Medical Center, Rotterdam, The Netherlands (B.S.P., R.V.V., R.D.V., J.D., A.M.R.).
authors: Richard
authors: R
authors: Van Veghel
authors: Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus MC, Erasmus University Medical Center, Rotterdam, The Netherlands (B.S.P., R.V.V., R.D.V., J.D., A.M.R.).
authors: René
authors: R
authors: De Vries
authors: Division of Cardiology and Pulmonology, Department of Interventional Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands (D.T.).
authors: Dennie
authors: D
authors: Tempel
authors: Division of Experimental Cardiology, Department of Cardiology, Thoraxcenter, Erasmus MC, Erasmus University Medical Center, Rotterdam, The Netherlands (S.S., H.V.B.).
authors: Stefan
authors: S
authors: Sneep
authors: Division of Experimental Cardiology, Department of Cardiology, Thoraxcenter, Erasmus MC, Erasmus University Medical Center, Rotterdam, The Netherlands (S.S., H.V.B.).
authors: Heleen
authors: H
authors: Van Beusekom
authors: Department of Immunology, Erasmus MC, Erasmus University Medical Center, Rotterdam, The Netherlands (V.J.V.D.V.).
authors: Vincent H J
authors: VH
authors: Van Der Velden
authors: Department of General and Interventional Cardiology, University Heart Center Hamburg Eppendorf, Germany (P.M.B., D.W.).
authors: Dirk
authors: D
authors: Westermann
authors: Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus MC, Erasmus University Medical Center, Rotterdam, The Netherlands (B.S.P., R.V.V., R.D.V., J.D., A.M.R.).
authors: A H Jan
authors: AH
authors: Danser
authors: Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus MC, Erasmus University Medical Center, Rotterdam, The Netherlands (B.S.P., R.V.V., R.D.V., J.D., A.M.R.).
authors: Anton J M
authors: AJ
authors: Roks
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000803:Angiotensin I / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology*; D000818:Animals; D006332:Cardiomegaly / Q000209:etiology / Q000517:prevention & control; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology; D005434:Flow Cytometry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects*; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D043925:Angiogenesis Inducing Agents; D010446:Peptide Fragments; D014665:Vasodilator Agents; D000803:Angiotensin I; C118790:angiotensin I (1-7)
keywords: angiotensin‐(1–7); cardiac function; endothelial progenitor cells; hemodynamics; myocardial infarction; renin–angiotensin system; vascular function
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