Highlights
- •Effect of estrogen replacing therapy (ERT) on cardiovascular events is controversial.
- •Investigate estrogen’s effects on vascular-resident stem/progenitor cells (VRS/Pc).
- •Estrogen can promote VRS/Pc proliferation and differentiation.
- •Thus, it functions to maintain homeostasis of vascular wall.
- •Older women does not benefit from ERT probably due to a shrink of VRS/Pc reservoir.
Abstract
Objectives: To investigate the effects of estrogen on growth and smooth muscle cell (SMC)-differentiation
of vascular wall-resident CD34+ stem/progenitor cells (VRS/Pcs). Methods and Results: The existence of CD34+ VRS/Pcs was confirmed by immunohistochemistry in the adventitia of arteries of young
(2-month-old) and old (24-month-old) female SD rats with less CD34+ adventitial cells detected in the old. The VRS/Pcs isolated from young animals were
grown in Stem cell growth medium or induced to differentiate into SMC with PDGF-BB
in the presence or absence of 17β-estrodiol (E2). Flow cytometry, RT-qPCR and Western blot showed that E2 promoted Brdu incorporation of the CD34+ VRS/Pcs growing in Stem cell growth medium; but when the cells were incubated in
PDGF-BB, the hormone enhanced their expression of SMC marker SM22. ChIP and IP assays
showed that E2 significantly promoted the binding of pELK1-SRF complex to the promoter of c-fos
gene in CD34+ VRS/Pcs growing in the Stem cell growth medium; but when the cells were stimulated
with PDGF-BB, an E2-enhanced binding of myocardin-SRF to the promoter of SM22 gene was found with enhanced
expression of SRC3 and its binding to myocardin. The effects of E2 above could be blocked by the estrogen receptor antagonist ICI 182,780 or inhibited
by SRF-siRNA. Conclusion: Estrogen has dual effects on CD34+ VRS/Pcs. For the undifferentiated VRS/Pcs, it accelerates their proliferation by
enhancing binding of pELK1-SRF complex to c-fos gene; while for the differentiating
VRS/Pcs, it promotes their differentiation to SMC through a mechanism of SRC3-mediated
interaction of myocardin-SRF complex with SM22 gene.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to AtherosclerosisAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- What the future holds for women after menopause: where we have been, where we are, and where we want to go.Climacteric. 2014; : 1-06
- The smooth muscle cell in culture.Physiol. Rev. 1979; 1: 1-61
- Smooth muscle phenotypic modulation–a personal experience.Arterioscler. Thromb. Vasc. Biol. 2012; 8: 1784-1789
- Vascular smooth muscle cell phenotype is defined by Ca2+-dependent transcription factors.FEBS J. 2013; 21: 5488-5499
- Phytoestrogen derivatives differentially inhibit arterial neointimal proliferation in a mouse model.Eur. J. Pharmacol. 2006; 1–3: 123-128
- Estrogen suppression of surgically induced vascular intimal hyperplasia in rabbits.J. Lab. Clin. Med. 1977; 1: 77-84
- Estradiol inhibition of arterial neointimal hyperplasia after balloon injury.J. Vasc. Surg. 1994; 4: 722-726
- Inhibition of myointimal hyperplasia and macrophage infiltration by estradiol in aorta allografts.Transplantation. 1991; 6: 967-972
- Endogenous estrogen deficiency reduces proliferation and enhances apoptosis-related death in vascular smooth muscle cells: insights from the aromatase-knockout mouse.Circulation. 2004; 4: 537-543
- Pregnancy-stimulated growth of vascular smooth muscle cells: importance of protein kinase C-dependent synergy between estrogen and platelet-derived growth factor.J. Cell. Physiol. 1996; 1: 22-32
- In vitro effect of oestradiol on thymidine uptake in pulmonary vascular smooth muscle cell: role of the endothelium.Br. J. Pharmacol. 1992; 3: 679-683
- Effect of estrogen on vascular smooth muscle cells is dependent upon cellular phenotype.Atherosclerosis. 1998; 1: 97-104
- Effects of estrogen on stress-induced premature senescence of vascular smooth muscle cells: a novel mechanism for the “time window theory” of menopausal hormone therapy.Atherosclerosis. 2011; 2: 294-300
- Dual effects of estrogen on vascular smooth muscle cells: receptor-mediated proliferative vs. metabolite-induced pro-senescent actions.Steroids. 2011; 3: 309-316
- Abundant progenitor cells in the adventitia contribute to atherosclerosis of vein grafts in ApoE-deficient mice.J. Clin. Invest. 2004; 9: 1258-1265
- Differentiation of multipotent vascular stem cells contributes to vascular diseases.Nat. Commun. 2012; 20123: 875
- Contribution of stem cells to neointimal formation of decellularized vessel grafts in a novel mouse model.Am. J. Pathol. 2012; 1: 362-373
- Comparative characterization of stromal vascular cells derived from three types of vascular wall and adipose tissue.Tissue Eng. Part A. 2013; 23–24: 2724-2734
- Human perivascular stem cells show enhanced osteogenesis and vasculogenesis with Nel-like molecule I protein.Tissue Eng. Part A. 2013; 11–12: 1386-1397
- Differentiation inhibiting activity (DIA/LIF) and mouse development.Dev. Biol. 1992; 2: 339-351
- SOCS1, SOCS3, and PIAS1 promote myogenic differentiation by inhibiting the leukemia inhibitory factor-induced JAK1/STAT1/STAT3 pathway.Mol. Cell. Biol. 2009; 18: 5084-5093
- Myocardin and ternary complex factors compete for SRF to control smooth muscle gene expression.Nature. 2004; 6979: 185-189
- Estrogen receptor-mediated activation of the serum response element in MCF-7 cells through MAPK-dependent phosphorylation of Elk-1.J. Biol. Chem. 2001; 15: 11590-11598
- 17beta-Estradiol induces cyclin D1 gene transcription, p36D1-p34cdk4 complex activation and p105Rb phosphorylation during mitogenic stimulation of G(1)-arrested human breast cancer cells.Oncogene. 1996; 11: 2315-2324
- Estrogen regulates activity of cyclin-dependent kinases and retinoblastoma protein phosphorylation in breast cancer cells.Mol. Endocrinol. 1996; 5: 488-498
- Annexin-1 regulates growth arrest induced by high levels of estrogen in MCF-7 breast cancer cells.Mol. Cancer Res. 2009; 2: 266-274
- Estrogen receptor beta inhibits human breast cancer cell proliferation and tumor formation by causing a G2 cell cycle arrest.Cancer Res. 2004; 1: 423-428
- Estrogen in obesity-associated colon cancer: friend or foe? protecting postmenopausal women but promoting late-stage colon cancer.Cancer Causes Control. 2012; 11: 1767-1773
- Effects of estrogen on diverse stem cells and relevant intracellular mechanisms.Sci. China Life Sci. 2010; 5: 542-547
- Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system.Science. 1992; 5052: 1707-1710
- Adult cardiac stem cells are multipotent and support myocardial regeneration.Cell. 2003; 6: 763-776
- Presence of vascular adventitial fibroblastic cells in diffuse-type gastric carcinomas.J. Clin. Pathol. 2004; 9: 970-972
- Characterisation of progenitor cells in human atherosclerotic vessels.Atherosclerosis. 2007; 2: 259-264
- Vascular wall resident progenitor cells: a source for postnatal vasculogenesis.Development. 2006; 8: 1543-1551
- G-protein-coupled estrogen receptor as a new therapeutic target for treating coronary artery disease.World J. Cardiol. 2014; 6: 367-375
- Regulatory role of G protein-coupled estrogen receptor for vascular function and obesity.Circ. Res. 2009; 104: 288-291
- Aldosterone mediates its rapid effects in vascular endothelial cells through GPER activation.Am. J. Physiol. Cell. Physiol. 2013; 304: C532-C540
- Activation of GPER induces differentiation and inhibition of coronary artery smooth muscle cell proliferation.PLoS One. 2013; 8: e64771
- GPR30 expression is required for the mineralocorticoid receptor-independent rapid vascular effects of aldosterone.Hypertension. 2011; 57: 442-451
- Estradiol-mediated ERK phosphorylation and apoptosis in vascular smooth muscle cells requires GPR 30.Am. J. Physiol. Cell. Physiol. 2009; 297: C1178-C1187
- Steroid receptor coactivator 3 is a coactivator for myocardin, the regulator of smooth muscle transcription and differentiation.Proc. Natl. Acad. Sci. U. S. A. 2007; 10: 4065-4070
Article info
Publication history
Published online: April 09, 2015
Accepted:
April 4,
2015
Received in revised form:
April 3,
2015
Received:
November 11,
2014
Identification
Copyright
© 2015 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
