INTRODUCTION: Angiotensin (Ang)-(1-7) is a recently identified vasoprotective heptapeptide, and it appears to activate the reparative functions of bone marrow-derived stem/progenitor cells (BMPCs). AIM: This study evaluated the effect of Ang-(1-7) in the angiogenic function of cavernosum in type 1 diabetes (T1D) and delineated the role of BMPCs in this protective function. METHODS: T1D was induced by streptozotocin in mice, and mice with 20-24 weeks of diabetes were used for the study. Ang-(1-7) was administered subcutaneously by using osmotic pumps. Cavernosa, and BMPCs from peripheral blood and bone marrow were evaluated in different assay systems. MAIN OUTCOME MEASURES: Angiogenic function was determined by endothelial tube formation in matrigel assay. Circulating BMPCs were enumerated by flow cytometry and proliferation was determined by BrdU incorporation. Cell-free supernatant of BMPCs were collected and tested for paracrine angiogenic effect. Expression of angiogenic factors in BMPCs and cavernosa were determined by real-time polymerase chain reaction. RESULTS: Ang-(1-7) (100 nM) stimulated angiogenesis in mouse cavernosum that was partially inhibited by Mas1 receptor antagonist, A779 (10 μM) (P < 0.05). In cavernosa of T1D, the angiogenic responses to Ang-(1-7) (P < 0.005) and VEGF (100 nM) (P < 0.03) were diminished. Ang-(1-7) treatment for 4 weeks reversed T1D-induced decrease in the VEGF-mediated angiogenesis. Ang-(1-7) treatment increased the circulating number of BMPCs and proliferation that were decreased in T1D (P < 0.02). Paracrine angiogenic function of BMPCs was reduced in diabetic BMPCs, which was reversed by Ang-(1-7). In diabetic BMPCs, SDF and angiopoietin-1 were upregulated by Ang-(1-7), and in cavernosum, VEGFR1, Tie-2, and SDF were upregulated and angiopoietin-2 was down-regulated. CONCLUSIONS: Ang-(1-7) stimulates angiogenic function of cavernosum in diabetes via its stimulating effects on both cavernosal microvasculature and BMPCs.
INTRODUCTION: Angiotensin (Ang)-(1-7) is a recently identified vasoprotective heptapeptide, and it appears to activate the reparative functions of bone marrow-derived stem/progenitor cells (BMPCs). AIM: This study evaluated the effect of Ang-(1-7) in the angiogenic function of cavernosum in type 1 diabetes (T1D) and delineated the role of BMPCs in this protective function. METHODS: T1D was induced by streptozotocin in mice, and mice with 20-24 weeks of diabetes were used for the study. Ang-(1-7) was administered subcutaneously by using osmotic pumps. Cavernosa, and BMPCs from peripheral blood and bone marrow were evaluated in different assay systems. MAIN OUTCOME MEASURES: Angiogenic function was determined by endothelial tube formation in matrigel assay. Circulating BMPCs were enumerated by flow cytometry and proliferation was determined by BrdU incorporation. Cell-free supernatant of BMPCs were collected and tested for paracrine angiogenic effect. Expression of angiogenic factors in BMPCs and cavernosa were determined by real-time polymerase chain reaction. RESULTS:Ang-(1-7) (100 nM) stimulated angiogenesis in mouse cavernosum that was partially inhibited by Mas1 receptor antagonist, A779 (10 μM) (P < 0.05). In cavernosa of T1D, the angiogenic responses to Ang-(1-7) (P < 0.005) and VEGF (100 nM) (P < 0.03) were diminished. Ang-(1-7) treatment for 4 weeks reversed T1D-induced decrease in the VEGF-mediated angiogenesis. Ang-(1-7) treatment increased the circulating number of BMPCs and proliferation that were decreased in T1D (P < 0.02). Paracrine angiogenic function of BMPCs was reduced in diabeticBMPCs, which was reversed by Ang-(1-7). In diabeticBMPCs, SDF and angiopoietin-1 were upregulated by Ang-(1-7), and in cavernosum, VEGFR1, Tie-2, and SDF were upregulated and angiopoietin-2 was down-regulated. CONCLUSIONS:Ang-(1-7) stimulates angiogenic function of cavernosum in diabetes via its stimulating effects on both cavernosal microvasculature and BMPCs.
Authors: Andrey C da Costa Gonçalves; Rodrigo A Fraga-Silva; Romulo Leite; Robson A S Santos Journal: Exp Physiol Date: 2012-10-05 Impact factor: 2.969
Authors: Yagna P R Jarajapu; Sergio Caballero; Amrisha Verma; Takahiko Nakagawa; Margaret C Lo; Qiuhong Li; Maria B Grant Journal: Invest Ophthalmol Vis Sci Date: 2011-07-07 Impact factor: 4.799
Authors: D Fedele; A Bortolotti; C Coscelli; F Santeusanio; L Chatenoud; E Colli; M Lavezzari; M Landoni; F Parazzini Journal: Int J Epidemiol Date: 2000-06 Impact factor: 7.196
Authors: Yagna P R Jarajapu; Ashay D Bhatwadekar; Sergio Caballero; Sugata Hazra; Vinayak Shenoy; Reinhold Medina; David Kent; Alan W Stitt; Catherine Thut; Eva M Finney; Mohan K Raizada; Maria B Grant Journal: Diabetes Date: 2012-12-10 Impact factor: 9.461
Authors: Brian R Hoffmann; Timothy J Stodola; Jordan R Wagner; Daniela N Didier; Eric C Exner; Julian H Lombard; Andrew S Greene Journal: Arterioscler Thromb Vasc Biol Date: 2017-01-12 Impact factor: 8.311
Authors: Goutham Vasam; Shrinidh Joshi; Sean E Thatcher; Stephen H Bartelmez; Lisa A Cassis; Yagna P R Jarajapu Journal: Diabetes Date: 2016-11-17 Impact factor: 9.461
Authors: S Foulquier; V Caolo; G Swennen; I Milanova; S Reinhold; C Recarti; N Alenina; M Bader; U M Steckelings; T Vanmierlo; M J Post; E A Jones; R J van Oostenbrugge; T Unger Journal: Angiogenesis Date: 2019-06-20 Impact factor: 9.596