Acute dilatation to phytoestrogens and estrogen receptor subtypes expression in small arteries from women with coronary heart disease

Cruz, María Natalia; Agewall, Stefan; Schenck‐Gustafsson, Karin; Kublickiene, Karolina

doi:10.1016/j.atherosclerosis.2007.01.038

Cited by 37 publications

(23 citation statements)

References 38 publications

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“…However, the increase of BP seen in SHRs may reflect microvascular dysfunction, and it is possible that, to inhibit hypertension, genistein targets ER-␤ expressed in resistance arteries (7). Interestingly, microvascular networks assessed by CD31 immunohistochemistry appeared to be defective within the group receiving vehicle but activated in the genistein-treated group of OVX SHRs.…”

Section: H270mentioning

confidence: 97%

Cardiac oxytocin receptor blockade stimulates adverse cardiac remodeling in ovariectomized spontaneously hypertensive rats

Jankowski

Wang

Danalache

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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An increasing amount of evidence demonstrates the beneficial role of oxytocin (OT) in the cardiovascular system. Similar actions are attributed to genistein, an isoflavonic phytoestrogen. The treatment with genistein activates the OT system in the aorta of ovariectomized (OVX) Sprague-Dawley (SD) rats. The objective of this study was to determine the effects of low doses of genistein on the OT-induced effects in rat hypertension. The hypothesis tested was that treatment of OVX spontaneously hypertensive rats (SHRs) with genistein improves heart structure and heart work through a mechanism involving the specific OT receptor (OTR). OVX SHRs or SD rats were treated with genistein (in g/g body wt sc, 10 days) in the presence or absence of an OT antagonist (OTA) [d(CH 2)5, Tyr(Me) 2 , Orn 8 ]-vasotocin or a nonspecific estrogen receptor antagonist (ICI-182780). Vehicle-treated OVX rats served as controls. RT-PCR and Western blot analysis demonstrated that left ventricular (LV) OTR, downregulated by ovariectomy, increased in response to genistein. In SHRs or SD rats, this effect was blocked by OTA or ICI-182780 administration. The OTR was mainly localized in microvessels expressing the CD31 marker and colocalized with endothelial nitric oxide synthase. In SHRs, the genistein-stimulated OTR increases were associated with improved fractional shortening, decreased blood pressure (12 mmHg), decreased heart weight-to-body weight ratio, decreased fibrosis, and lowered brain natriuretic peptide in the LV. The prominent finding of the study is the detrimental effect of OTA treatment on the LV of SHRs. OTA treatment of OVX SHRs resulted in a dramatic worsening of ejection fractions and an augmented fibrosis. In conclusion, these results demonstrate that cardiac OTRs are involved in the regulation of cardiac function of OVX SHRs. The decreases of OTRs may contribute to cardiac pathology following menopause. oxytocin receptor; ovariectomy; hypertrophy; genistein THE BIOLOGICAL ACTIVITIES of oxytocin (OT) are associated with reproductive functions, such as uterine contraction, milk ejection, and maternal care. More recently, OT has been found to regulate vascular tone, blood pressure (BP), and kidney function (16). The pathophysiological roles of OT action in the cardiovascular system are beginning to be understood. The heart is a site of OT synthesis and action (15,21,22). In the adult rat heart, OT receptors (OTRs) are mainly expressed in endothelial cells and in cardiomyocytes (21). OTR activation in the heart stimulates cardioprotective reactions, such as negative inotropy and chronotropy, parasympathetic neuromodulation, and the release of atrial natriuretic peptide (ANP) (15) and nitric oxide (NO) (33). OTR-specific signaling induces the differentiation of embryonic stem cells that have been shown to convert to cardiac muscle cells (8,21,35). Recently, we observed that OT increases glucose uptake in cardiomyocytes via the cardioprotective phosphoinositide 3-kinase (PI3K) pathway and potentiates the glucose uptake effect of ...

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Section: H270mentioning

confidence: 97%

Cardiac oxytocin receptor blockade stimulates adverse cardiac remodeling in ovariectomized spontaneously hypertensive rats

Jankowski

Wang

Danalache

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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“…Tamoxifen is an example of a ligand being an agonist in tissues where coactivators predominate (via GPER), but antagonistic where corepressors dominate (via ERα and β). Phytoestrogens (genistein, resveratrol) act as ER agonist in vasculature, but antagonist in breast and uterine tissue 35 , and have been shown to cause acute relaxation in arteries of postmenopausal women with CHD versus healthy controls, whereas in healthy controls PPT (selective ERα agonist) causes more relaxation than E2 35 . This suggests selectively targeting GPER or perhaps ERα46 could therefore uncouple the vascular beneficial and undesirable effects of estrogen.…”

Section: Discussionmentioning

confidence: 99%

Increased estrogen receptor alpha expression in experimental aortic aneurysms in females compared with males

Laser

Ghosh

Roelofs

et al. 2010

Journal of the American College of Surgeons

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“…isoflavones has a protective effect on cardiovascular and cerebrovascular diseases [13,14]. Genistein [15] is the most abundant phytoestrogen present in soybean isoflavones.…”

Section: Studies From Epidemiological Investigations Have Indicated Tmentioning

confidence: 99%

Genistein suppresses smooth muscle cell-derived foam cell formation through tyrosine kinase pathway

Lin

Zhao

et al. 2015

Biochemical and Biophysical Research Communications

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Acute dilatation to phytoestrogens and estrogen receptor subtypes expression in small arteries from women with coronary heart disease

Cited by 37 publications

References 38 publications

Cardiac oxytocin receptor blockade stimulates adverse cardiac remodeling in ovariectomized spontaneously hypertensive rats

Cardiac oxytocin receptor blockade stimulates adverse cardiac remodeling in ovariectomized spontaneously hypertensive rats

Increased estrogen receptor alpha expression in experimental aortic aneurysms in females compared with males

Genistein suppresses smooth muscle cell-derived foam cell formation through tyrosine kinase pathway

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