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A role for Angiotensin‐(1‐7) and its receptors in sprouting angiogenesis and vascular homeostasis
Author(s) -
Grant Gary,
Bernadoni Juliana Lech,
Soh Hong Jie,
Walther Thomas
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.05163
Subject(s) - angiogenesis , homeostasis , medicine , receptor , progenitor cell , matrigel , vasculogenesis , endocrinology , angiotensin ii , biology , microbiology and biotechnology , endothelial stem cell , in vivo , chemistry , stem cell , in vitro , biochemistry
Background Angiotensin converting enzyme 2 converts angiotensin (Ang) II into the biologically active heptapeptide Ang‐(1‐7). We have previously shown that Ang‐(1‐7) is involved in the stimulation and homeostasis of circulating endothelial progenitor cells, and that Ang‐(1‐7) is an endogenous ligand for the G protein‐coupled receptors Mas and MrgD. To better understand the role of the peptide in endothelial cell biology and homeostasis and the receptors involved, we aimed to investigate the effect of Ang‐(1‐7) on various functional parameters of endothelial cells. Methods and Results Ang‐(1‐7) was just as effective as vascular endothelial growth factor (VEGF) at stimulating endothelial tube formation in an in‐vitro Matrigel based assay in HUVEC. To investigate the effects in a more physiological model, we isolated aortas from Mas, MrgD, and Mas/MrgD deficient animals together with age and gender matched controls in an ex‐vivo model of sprouting. While aortas with a deficiency in either Mas or MrgD still showed normal number and length of sprouts as wild type mice, aortic rings deficient for Mas/MrgD showed a reduction in sprout length by 87% and no of sprouts by 77% when compared with wild type controls. We were also able to show that Mas deficient mice had a reduction in circulating CD34+ cells, a marker for heamopoeitic stem cells. Finally, we were able to show that after shunting blood flow to the hind limb of mice in an in‐vivo hind limb ischemia assay, Ang‐(1‐7) was able to restore 62.2% of blood flow in comparison with 17.1% in solvent‐treated mice. Conclusion All together, our data suggest a key role for Ang‐(1‐7) and its receptors in sprouting angiogenesis, vascular homeostasis, and thus might be a promising new option for the treatment of peripheral vascular disease.