Intramuscular administration of estrogen may promote angiogenesis and perfusion in a rabbit model of chronic limb ischemia

Kyriakides, Zenon S.; Petinakis, Pantelis; Kaklamanis, Loukas; Sbarouni, Eftihia; Karayannakos, P.; Iliopoulos, Dimitrios; Dontas, Ismene; Kremastinos, Dimitrios Th.

doi:10.1016/s0008-6363(00)00199-1

Cited by 46 publications

(31 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, in the animal model used in the present study, fractured bones were healed in most of the animals by day 72. Although estrogen has been shown to stimulate angiogenesis in skeletal muscles (Kyriakides et al 2001), we observed a slight increase in capillary density in D and 4-MBC treated rats, but not in the estrogen supplemented animals after 36 days of fracture healing. On the other hand, the estrogenic effect of the substances may facilitate the animals to restore their physical activity more rapidly.…”

Section: Analyses Of Musclecontrasting

confidence: 81%

“…In muscles of mature female rodents, estrogen has been associated with modulation of muscle fiber types (Kadi et al 2002, Feng et al 2004, whereas, the crosssectional areas of all types of fibers were not affected by estrogen status (McClung et al 2006, Moran et al 2007. Moreover, estrogen has been reported to promote angiogenesis in skeletal muscles of estrogen deficient animals (Kyriakides et al 2001).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effect of daidzein, 4-methylbenzylidene camphor or estrogen on gastrocnemius muscle of osteoporotic rats undergoing tibia healing period

Komrakova¹,

Werner²,

Wicke³

et al. 2009

Journal of Endocrinology

View full text Add to dashboard Cite

The effect of daidzein (D), 4-methylbenzylidene camphor (4-MBC) or estradiol-17b-benzoate (E 2 ) on muscle of osteoporotic rats during fracture healing was studied. After performing a metaphyseal tibia osteotomy in 96 osteoporotic 5-month-old female Sprague-Dawley rats, they received daily 50 mg D, 200 mg 4-MBC or 0 . 4 mg E 2 per kg body weight, or soy free (SF) diet up to 36 and 72 days. Mitochondrial activity, fiber area, and capillary density were analyzed in M. gastrocnemius. Osseous callus bridging of fracture was observed in half of the rats after 36 days. By day 72, fracture was healed in most of the animals. State 3 mitochondrial respiration significantly enhanced in E 2 , 4-MBC and D groups versus SF after 36 days (30, 32 and 32 vs 23 pmol O 2 /s per mg). It declined after 72 days, however, in E 2 group it was still at a higher level versus SF (25, 23 and 21 vs 20 pmol O 2 /s per mg). Size of fast oxidative glycolytic (FOG) and fast glycolytic (FG) fibers, capillary density did not differ significantly between the groups, however, at day 36 an increase in D and 4-MBC groups was detectable. FOG diameter was 64, 66, 68, and 58 mm and FG diameter was 88, 98, 95, and 89 mm in SF, D, 4-MBC, and E 2 groups. The ratio of capillaries to muscle fiber was 1 . 1, 1 . 4, 1 . 3, and 1 . 1 in SF, D, 4-MBC and E 2 groups by day 36. D and 4-MBC react similar to estrogen thereby improving oxidative cell metabolism in severe osteoporotic rats. The level of mitochondrial activity was higher, though no significant morphological differences could be shown.

show abstract

Section: Analyses Of Musclecontrasting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Effect of daidzein, 4-methylbenzylidene camphor or estrogen on gastrocnemius muscle of osteoporotic rats undergoing tibia healing period

Komrakova¹,

Werner²,

Wicke³

et al. 2009

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…8 Estrogen enhances endothelial cell activities in vitro 1,9 and has favorable effects on ischemic neovascularization in vivo. 10,11 In human studies, it was reported that postmenopausal hormone replacement therapy was associated with reduced risk of mortality after myocardial infarction (MI). 12 Tissue ischemia induces upregulation of angiogenic growth factors and mobilization of circulating cellular elements that together enable development of an accessory vasculature for organ survival.…”

Section: Editorial P 2203 Clinical Perspective P 2270mentioning

confidence: 99%

Estrogen Receptors α and β Mediate Contribution of Bone Marrow–Derived Endothelial Progenitor Cells to Functional Recovery After Myocardial Infarction

et al. 2006

View full text Add to dashboard Cite

Background-Estradiol (E 2 ) modulates the kinetics of circulating endothelial progenitor cells (EPCs) and favorably affects neovascularization after ischemic injury. However, the roles of estrogen receptors ␣ (ER␣) and ␤ (ER␤) in EPC biology are largely unknown. Methods and Results-In response to E 2 , migration, tube formation, adhesion, and estrogen-responsive elementdependent gene transcription activities were severely impaired in EPCs obtained from ER␣-knockout mice (ER␣KO) and moderately impaired in ER␤KO EPCs.

show abstract

“…7 A candidate mechanism of cerebral protection is the ability of E2 to modulate angiogenesis. 8 -11 E2-mediated angiogenesis occurs in normal tissues (eg, female reproductive tract 8,9,12 , retina, 10 and other nonreproductive tissues) 11 as well as pathologic conditions (eg, experimental limb ischemia, 13 tumors, 8 and aging brain). 14 Enhancement of angiogenesis is an attractive property.…”

mentioning

confidence: 99%

Estradiol Regulates Angiopoietin-1 mRNA Expression Through Estrogen Receptor-α in a Rodent Experimental Stroke Model

Ardelt

McCullough

Korach

et al. 2005

Stroke

View full text Add to dashboard Cite

Background and Purpose-Female, compared with male, animals are protected from cerebral ischemic injury.Physiological concentrations of 17␤-estradiol (E2) reduce damage in experimental stroke. E2 augments angiogenesis in reproductive organs and noncerebral vascular beds. We hypothesized that E2 protects brain in stroke through modulation of angiogenesis. We quantified molecular markers of angiogenesis and capillary density before and after unilateral middle cerebral artery occlusion (MCAO). Methods-Female animals were ovariectomized, treated with 25 g E2 or placebo implants, and subjected to 2-hour MCAO and 22 hours of reperfusion. Brain angiopoietin-1 (Ang-1), Ang-2, Tie-1, Tie-2, vascular endothelial growth factor (VEGF), VEGF R1, and VEGF R2 mRNA levels were determined by RNAse protection assays, and CD31-positive vessels were counted. Results-E2, but not ischemia, upregulated cerebral Ang-1 mRNA by 49%. Capillary density was higher in the brains of E2-treated animals. In estrogen receptor-␣ knockout (ERKO) mice, E2-mediated induction of Ang-1 mRNA was absent relative to wild-type littermates. Conclusions-These results suggest that E2 increases Ang-1 and enhances capillary density in brain under basal conditions, priming the MCA territory for survival after experimental focal ischemia. Key Words: angiogenesis Ⅲ cerebrovascular accident Ⅲ endothelial growth factors W omen are protected from stroke relative to men; this advantage is lost with menopause. In 2002, the combined estrogen-progestin arm of the Women's Health Initiative was stopped because of lack of efficacy in cardiovascular disease prevention, including stroke. 1 The estrogen-alone arm of the trial was discontinued because of increased stroke risk in hormone users. 2 Therefore, data from animals and cultured cells are under intense scrutiny to elucidate biological pathways of the effects of 17␤-estradiol (E2) in brain and cerebral vasculature. The cellular and molecular pathophysiology of cerebral ischemia is strongly influenced by gender and female sex steroids. Although the preventative role of E2 is unclear, it does reduce stroke sensitivity (ie, attenuates neuronal damage once ischemia occurs). [3][4][5][6] The mechanism of protection is likely multifactorial. 4 E2 signals through estrogen receptor-␣ (ER␣) and ER␤ to alter gene expression. 4 Rodent brains express both receptors, but ER␣ functions in E2-mediated protection in stroke. 7 A candidate mechanism of cerebral protection is the ability of E2 to modulate angiogenesis. 8 -11 E2-mediated angiogenesis occurs in normal tissues (eg, female reproductive tract 8,9,12 , retina, 10 and other nonreproductive tissues) 11 as well as pathologic conditions (eg, experimental limb ischemia, 13 tumors, 8 and aging brain). 14 Enhancement of angiogenesis is an attractive property. Improvement of collateral blood flow through angiogenesis or other endothelial-based adaptive mechanisms may occur after transient ischemic attacks, before stroke, in patients with intracranial stenosis. 15 Such patients may be pr...

show abstract

Intramuscular administration of estrogen may promote angiogenesis and perfusion in a rabbit model of chronic limb ischemia

Abstract: Administration of estrogen promotes angiogenesis and perfusion in ischemic rabbit hindlimbs. Thus, estrogen may represent a new therapeutic modality in the management of arterial insufficiency.

Cited by 46 publications

References 22 publications

Effect of daidzein, 4-methylbenzylidene camphor or estrogen on gastrocnemius muscle of osteoporotic rats undergoing tibia healing period

Effect of daidzein, 4-methylbenzylidene camphor or estrogen on gastrocnemius muscle of osteoporotic rats undergoing tibia healing period

Estrogen Receptors α and β Mediate Contribution of Bone Marrow–Derived Endothelial Progenitor Cells to Functional Recovery After Myocardial Infarction

Estradiol Regulates Angiopoietin-1 mRNA Expression Through Estrogen Receptor-α in a Rodent Experimental Stroke Model

Contact Info

Product

Resources

About