Estradiol-induced, endothelial progenitor cell-mediated neovascularization in male mice with hind-limb ischemia

Ruifrok, Willem-Peter T.; Boer, Rudolf A. de; Iwakura, Atsushi; Silver, Marcy; Kusano, Kengo; Tio, René A.; Losordo, Douglas W.

doi:10.1177/1358863x08096666

Cited by 40 publications

(20 citation statements)

References 53 publications

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“…Previous studies indicate that the application of estradiol or phytoestrogen stimulates the mobilization of EPCs from the bone marrow. 49,50 On the other hand, Robb et al 51 analyzed the numbers of circulating EPCs during the menstrual cycle and found that there is no clear link between EPCs and blood concentrations of sex steroids. Similar results were reported by Webster et al, 52 who did not detect any fluctuations of EPCs across the menstrual, follicular, periovulatory, and luteal phase of the menstrual cycle of healthy women, whereas EPC levels varied considerably between individual subjects.…”

Section: Epcs In Endometriosismentioning

confidence: 98%

Estrogen Stimulates Homing of Endothelial Progenitor Cells to Endometriotic Lesions

Rudzitis‐Auth

Nenicu

Nickels

et al. 2016

The American Journal of Pathology

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The incorporation of endothelial progenitor cells (EPCs) into microvessels contributes to the vascularization of endometriotic lesions. Herein, we analyzed whether this vasculogenic process is regulated by estrogen. Estrogen- and vehicle-treated human EPCs were analyzed for migration and tube formation. Endometriotic lesions were induced in irradiated FVB/N mice, which were reconstituted with bone marrow from FVB/N-TgN (Tie2/green fluorescent protein) 287 Sato mice. The animals were treated with 100 μg/kg β-estradiol 17-valerate or vehicle (control) over 7 and 28 days. Lesion growth, cyst formation, homing of green fluorescent protein(+)/Tie2(+) EPCs, vascularization, cell proliferation, and apoptosis were analyzed by high-resolution ultrasonography, caliper measurements, histology, and immunohistochemistry. Numbers of blood circulating EPCs were assessed by flow cytometry. In vitro, estrogen-treated EPCs exhibited a higher migratory and tube-forming capacity when compared with controls. In vivo, numbers of circulating EPCs were not affected by estrogen. However, estrogen significantly increased the number of EPCs incorporated into the lesions' microvasculature, resulting in an improved early vascularization. Estrogen further stimulated the growth of lesions, which exhibited massively dilated glands with a flattened layer of stroma. This was mainly because of an increased glandular secretory activity, whereas cell proliferation and apoptosis were not markedly affected. These findings indicate that vasculogenesis in endometriotic lesions is dependent on estrogen, which adds a novel hormonally regulated mechanism to the complex pathophysiology of endometriosis.

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Section: Epcs In Endometriosismentioning

confidence: 98%

Estrogen Stimulates Homing of Endothelial Progenitor Cells to Endometriotic Lesions

Rudzitis‐Auth

Nenicu

Nickels

et al. 2016

The American Journal of Pathology

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“…Deprivation of endogenous estrogen (130,(147)(148) and synthetic estrogen supplementation (131,(149)(150) have opposite potent vasoactive effects, although the relationship between the osteogenic and cardiovascular effects remains to be fully elucidated.…”

Section: Physiological and Pharmacological Regulators Of Bone Perfusionmentioning

confidence: 99%

The Key Role of the Blood Supply to Bone

2013

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The importance of the vascular supply for bone is well-known to orthopaedists but is still rather overlooked within the wider field of skeletal research. Blood supplies oxygen, nutrients and regulatory factors to tissues, as well as removing metabolic waste products such as carbon dioxide and acid. Bone receives up to about 10% of cardiac output, and this blood supply permits a much higher degree of cellularity, remodelling and repair than is possible in cartilage, which is avascular. The blood supply to bone is delivered to the endosteal cavity by nutrient arteries, then flows through marrow sinusoids before exiting via numerous small vessels that ramify through the cortex. The marrow cavity affords a range of vascular niches that are thought to regulate the growth and differentiation of hematopoietic and stromal cells, in part via gradients of oxygen tension. The quality of vascular supply to bone tends to decline with age and may be compromised in common pathological settings, including diabetes, anaemias, chronic airway diseases and immobility, as well as by tumours. Reductions in vascular supply are associated with bone loss. This may be due in part to the direct effects of hypoxia, which blocks osteoblast function and bone formation but causes reciprocal increases in osteoclastogenesis and bone resorption. Common regulatory factors such as parathyroid hormone or nitrates, both of which are potent vasodilators, might exert their osteogenic effects on bone via the vasculature. These observations suggest that the bone vasculature will be a fruitful area for future research.

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“…Interestingly, ovariectomized female mice do not benefi t from exogenous DHT treatment following ischemia [ 38 ]. In contrast to this, male mice receiving estrogen treatment recover faster from hind limb ischemic injury than placebo-treated mice through progenitor cell recruitment [ 45 ].…”

Section: Sex Specifi City Of Steroid Actionsmentioning

confidence: 98%

Role of Sex Steroids in Angiogenesis

Lecce

Lam

2013

Biochemical Basis and Therapeutic Implications of Angiogenesis

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Sex steroids such as estrogen and testosterone are key mediators of angiogenesis. They are implicated in both physiological and pathological angiogenesis such as during the menstrual cycle, wound healing, and cancer growth and progression. Sex steroids regulate many aspects of angiogenesis through both classic genomic signaling pathways which regulate gene expression and also rapid action nongenomic pathways. In this capacity, sex steroids are able to modulate endothelial and progenitor cell functions such as proliferation, migration, and attachment, which are all essential components involved in neovascularization. Since sex steroids are known to augment angiogenesis which is vital to tumor progression and growth, common treatment of hormone-responsive tumors is through sex steroid receptor antagonists. Due to the involvement of sex steroids in necessary physiological functions as well as the potential to promote pathological angiogenesis, it is fundamental that the mechanisms behind sex steroid-mediated neovascularization are understood.

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Estradiol-induced, endothelial progenitor cell-mediated neovascularization in male mice with hind-limb ischemia

Cited by 40 publications

References 53 publications

Estrogen Stimulates Homing of Endothelial Progenitor Cells to Endometriotic Lesions

Estrogen Stimulates Homing of Endothelial Progenitor Cells to Endometriotic Lesions

The Key Role of the Blood Supply to Bone

Role of Sex Steroids in Angiogenesis

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