Effect of a stable Angiotensin-(1-7) analogue on progenitor cell recruitment and cardiovascular function post myocardial infarction

TY - JOUR

T1 - Effect of a stable Angiotensin-(1-7) analogue on progenitor cell recruitment and cardiovascular function post myocardial infarction

AU - Sevá Pessôa, Bruno

AU - Becher, Peter Moritz

AU - Van Veghel, Richard

AU - De Vries, René

AU - Tempel, Dennie

AU - Sneep, Stefan

AU - Van Beusekom, Heleen

AU - Van Der Velden, Vincent H J

AU - Westermann, Dirk

AU - Danser, A H Jan

AU - Roks, Anton J M

N1 - © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

PY - 2015/2/5

Y1 - 2015/2/5

N2 - 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.METHODS AND 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.

AB - 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.METHODS AND 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.

KW - Angiogenesis Inducing Agents/pharmacology

KW - Angiotensin I/administration & dosage

KW - Animals

KW - Cardiomegaly/etiology

KW - Disease Models, Animal

KW - Endothelial Cells/drug effects

KW - Flow Cytometry

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Myocardial Infarction/complications

KW - Myocytes, Cardiac/drug effects

KW - Peptide Fragments/administration & dosage

KW - Stem Cells/cytology

KW - Time Factors

KW - Vasodilator Agents/pharmacology

U2 - 10.1161/JAHA.114.001510

DO - 10.1161/JAHA.114.001510

M3 - SCORING: Journal article

C2 - 25655571

VL - 4

SP - e001510

JO - J AM HEART ASSOC

JF - J AM HEART ASSOC

SN - 2047-9980

IS - 2

ER -