phytoestrogens and Ischemia

Prior studies linked higher blood phytoestrogen (phytoE) levels of daidzein to beneficial lipoprotein profiles, and higher genistein levels related to worse coronary microvascular dysfunction in women with suspected ischemic heart disease (IHD). However, relationships to adverse outcomes remain unclear. We investigated the associations between eight serum phytoE and major adverse cardiac events (MACE) including myocardial infarction, stroke, hospitalization for heart failure and angina, cardiovascular and all-cause mortality, in women undergoing functional coronary angiography (FCA) for suspected ischemia.. We evaluated 143 women enrolled in the Women's Ischemia Syndrome Evaluation (1996-2001) for serum phytoE levels and 10-year outcomes. Median follow-up duration was 6.08 years (range 0.01-8.16) for time to MACE and 9.11 years (range 0.01-11.08 years) for time to death. Kaplan-Meier plots were analyzed and Cox regression models adjusted for age, body mass index, hypertension, diabetes, dyslipidemia and tobacco use.. The median age was 54.7 (range 20.6-76.1) years and BMI was 29.3 (range 18.4-57.2). Of the cohort, 80.4% had nonobstructive coronary artery disease, 56% had hypertension, 22.4% had diabetes, 58.1% had dyslipidemia and 59.4% of the women used tobacco. Each unit decrease in log glycitin was associated with increased MACE hazard (HR 1.97, 95% [CI 1.23, 3.14], p = 0.005). Glycitin absence was associated with earlier angina hospitalization (log rank p = 0.05). After 6 years, MACE increased with each unit decrease in log genistein (HR 6.17, 95% [CI 1.81, 20.8], p = 0.0036). Other phytoE did not show statistically significant associations with outcomes.. Among women with suspected IHD undergoing clinically indicated invasive FCA, low serum glycitin was associated with increased MACE and earlier angina hospitalization, while low genistein was associated with increased MACE after 6 years. Future studies are needed regarding phytoE, nutrition, outcomes and possibly supplementation.

Topics: Adult; Aged; Coronary Angiography; Coronary Artery Disease; Female; Humans; Ischemia; Middle Aged; Myocardial Ischemia; Phytoestrogens; Prognosis; Risk Factors; Young Adult

Aucubin (AU) is an iridoid glycoside that has been shown to display estrogenic properties and has various pharmacological effects. Herein, we described the angiogenic properties of AU. In the study, hindlimb ischemia was induced by ligation of femoral artery on the right leg of ovariectomized mice. AU treatment significantly accelerated perfusion recovery and reduced tissue injury in mice muscle. Quantification of CD31-positive vessels in hindlimb muscles provided evidences that AU promoted angiogenesis in peripheral ischemia. In addition, results from quantitative PCR and western blot suggested AU induced angiogenesis via vascular endothelial cell growth factor (VEGF)/Akt/endothelial nitric oxide synthase (eNOS) signaling pathway. More interestingly, AU's angiogenic effects could be completely abolished in estrogen receptor beta (ERβ) knockout mice. In conclusion, the underlying mechanisms were elucidated that AU produced pro-angiogenic effects through ERβ-mediated VEGF signaling pathways. These results expand knowledge about the beneficial effects of AU in angiogenesis and blood flow recovery. It might provide insight into the ERβ regulating neovascularisation in hindlimb ischemia and identify AU as a potent new compound used for the treatment of peripheral vascular disease.

Topics: Angiogenesis Inducing Agents; Animals; Disease Models, Animal; Estrogen Receptor beta; Female; Femoral Artery; Gene Expression Regulation; Hindlimb; Iridoid Glucosides; Ischemia; Ligation; Mice; Mice, Inbred C57BL; Mice, Knockout; Neovascularization, Physiologic; Nitric Oxide Synthase Type III; Ovariectomy; Phytoestrogens; Platelet Endothelial Cell Adhesion Molecule-1; Proto-Oncogene Proteins c-akt; Recovery of Function; Signal Transduction; Vascular Endothelial Growth Factor A

Genistein, a naturally occurring isoflavonic phytoestrogen associated with reduced incidence of heart disease, may be a possible alternative treatment for postmenopausal women with heart disease.. This study examined the effects of genistein on in vitro heart function and ischemic tolerance in ovariectomized (OVX) Sprague-Dawley rats.. To examine the acute effects of genistein on cardiac function, isolated working hearts were perfused under aerobic conditions with increasing concentrations of genistein (10-150 microM). A separate group of OVX rats was used to assess ischemic tolerance: treated rats received genistein (250 mg/kg, dissolved in 200 microL dimethyl sulfoxide [DMSO]) injected once daily for 2 days, and control rats received DMSO only. After treatment, hearts were perfused for 30 minutes under aerobic conditions and then subjected to 20 minutes of global no-flow ischemia by clamping the preload and afterload lines, followed by 30 minutes of reperfusion.. Genistein was associated with improvements in mechanical function in OVX rat hearts (n = 5) with maximum increases in contractility (259 mm Hg/sec above baseline) and cardiac output (7 mL/min above baseline) observed with 30 microM of genistein (both, P < 0.05). Relative to baseline, genistein-treated hearts (n = 5) also had greater ischemic tolerance than did control hearts (n = 6) and significant improvements in mean (SEM) recovery of contractility (to 75.0% [9.7%] of preischemic function; P < 0.05) and cardiac output (to 48.8% [12.3%] of preischemic function; P < 0.05) after reperfusion. These effects occurred without significant changes in myocardial levels of nonprotein thiols or thiobarbituric acid reactive substances, although a reduction in mean glucose transporter protein 4 content (13.2% [2.7%]; P < 0.05) was observed in genistein-treated hearts. No significant changes in blood pressure were observed with genistein.. Despite the lack of significant changes in physical characteristics, 2-day treatment with genistein was associated with significant cardioprotective effects in OVX rats, suggesting a potential therapeutic role in postmenopausal women.

Topics: Animals; Disease Models, Animal; Female; Genistein; In Vitro Techniques; Ischemia; Myocardial Contraction; Ovariectomy; Phytoestrogens; Postmenopause; Rats; Rats, Sprague-Dawley