ACE2/ACE imbalance and impaired vasoreparative functions of stem/progenitor cells in aging
- 1 June 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in GeroScience
- Vol. 43 (3), 1423-1436
- https://doi.org/10.1007/s11357-020-00306-w
Abstract
Aging increases risk for ischemic vascular diseases. Bone marrow-derived hematopoietic stem/progenitor cells (HSPCs) are known to stimulate vascular regeneration. Activation of either the Mas receptor (MasR) by angiotensin-(1-7) (Ang-(1-7)) or angiotensin-converting enzyme-2 (ACE2) stimulates vasoreparative functions in HSPCs. This study tested if aging is associated with decreased ACE2 expression in HSPCs and if Ang-(1-7) restores vasoreparative functions. Flow cytometric enumeration of Lin(-)CD45(low)CD34(+) cells was carried out in peripheral blood of male or female individuals (22-83 years of age). Activity of ACE2 or the classical angiotensin-converting enzyme (ACE) was determined in lysates of HSPCs. Lin(-)Sca-1(+)cKit(+) (LSK) cells were isolated from young (3-5 months) or old (20-22 months) mice, and migration and proliferation were evaluated. Old mice were treated with Ang-(1-7), and mobilization of HSPCs was determined following ischemia induced by femoral ligation. A laser Doppler blood flow meter was used to determine blood flow. Aging was associated with decreased number (Spearman r = - 0.598, P < 0.0001, n = 56), decreased ACE2 (r = - 0.677, P < 0.0004), and increased ACE activity (r = 0.872, P < 0.0001) (n = 23) in HSPCs. Migration or proliferation of LSK cells in basal or in response to stromal-derived factor-1 alpha in old cells is attenuated compared to young, and these dysfunctions were reversed by Ang-(1-7). Ischemia increased the number of circulating LSK cells in young mice, and blood flow to ischemic areas was recovered. These responses were impaired in old mice but were restored by treatment with Ang-(1-7). These results suggest that activation of ACE2 or MasR would be a promising approach for enhancing ischemic vascular repair in aging.Funding Information
- National Institute on Aging (AG056881)
- National Institute of General Medical Sciences (P30-GM 103332-01)
This publication has 59 references indexed in Scilit:
- Impact of ACE2 Deficiency and Oxidative Stress on Cerebrovascular Function With AgingStroke, 2012
- Angiotensin-(1–7) Administration Reduces Oxidative Stress in Diabetic Bone MarrowEndocrinology, 2012
- Blockade of NADPH Oxidase Restores Vasoreparative Function in Diabetic CD34+CellsInvestigative Ophthalmology & Visual Science, 2011
- Chronic treatment with angiotensin‐(1‐7) improves renal endothelial dysfunction in apolipoproteinE‐deficient miceBritish Journal of Pharmacology, 2011
- Hypoxia differentially regulates VEGFR1 and VEGFR2 levels and alters intracellular signaling and cell migration in endothelial cellsBiochemical and Biophysical Research Communications, 2011
- Aging Is Not Associated With Bone Marrow-Resident Progenitor Cell DepletionThe Journals of Gerontology, Series A: Biological Sciences and Medical Sciences, 2010
- Hypoxic Preconditioning Enhances the Benefit of Cardiac Progenitor Cell Therapy for Treatment of Myocardial Infarction by Inducing CXCR4 ExpressionCirculation Research, 2009
- Aging and Diabetes Impair the Neovascular Potential of Adipose-Derived Stromal CellsPlastic and Reconstructive Surgery, 2009
- Murine Model of Hindlimb IschemiaJournal of Visualized Experiments, 2009
- Angiotensin-(1-7) Through Receptor Mas Mediates Endothelial Nitric Oxide Synthase Activation via Akt-Dependent PathwaysHypertension, 2007