Acute dilatation to phytoestrogens and estrogen receptor subtypes expression in small arteries from women with coronary heart disease.
We tested if endothelial function and estrogen receptor (ER) expression differs between resistance arteries in subcutaneous circulation from postmenopausal women with coronary heart disease (CHD, congruent with 1 year after myocardial infarction, n=12) and aged matched controls (n=14); and if acute effects of phytoestrogens (genistein, resveratrol) could be of relevance for vascular protection. We utilized ex vivo small artery ( congruent with 350 microm) bioassays and found no difference in bradykinin (BK)-mediated dilatation between the groups. One-hour incubation with phytoestrogens (natural ER beta agonists), propyl-pyrazole-triol-trisphenol (PPT-selective ER alpha agonist) and 17beta-estradiol (17beta-E(2)-ER alpha/beta agonist) at 0.01 microM/L had no effect on BK-induced responses. Concentration-response curves (0.01-30 microM/L) to investigated compounds were also obtained and compared in separate arteries. We found that dilatation to phytoestrogens was enhanced in CHD if compared to controls (p<0.05), while responses to 17beta-E(2) remained similar. The dilatation to phytoestrogens was also higher if compared to 17beta-E(2) (p<0.05) in CHD. In controls, only responses to PPT, but not to phytoestrogens, were enhanced in comparison to 17beta-E(2) (p<0.05). Inhibition of NO synthase had no effect on dilatation induced by increasing concentrations of investigated compounds. ER beta expression was enhanced in the vascular wall from CHD women, while ER alpha predominated in the controls (p<0.05). We suggest that diet supplementation by phytoestrogens may provide cardiovascular benefit for postmenopausal women with CHD. The selective targeting of one of the ER subtype may have implications for women's cardiovascular health.
Cruz
Maria Natalia
MN
Karolinska Institutet, Institution for Clinical Science Intervention and Technology (CLINTEC), Division of Obstetrics and Gynecology, Karolinska University Hospital, Huddinge Campus, 14186 Stockholm, Sweden.
Agewall
Stefan
S
Karolinska Institutet, Department of Cardiology, Karolinska University Hospital, Huddinge Campus, 14186 Stockholm, Sweden.
Schenck-Gustafsson
Karin
K
Karolinska Institutet, Department of Cardiology, Karolinska University Hospital, Solna, Huddinge Campus, 14186 Stockholm, Sweden.
Kublickiene
Karolina
K
Karolinska Institutet, Institution for Clinical Science Intervention and Technology (CLINTEC), Division of Obstetrics and Gynecology, Karolinska University Hospital, Huddinge Campus, 14186 Stockholm, Sweden. Electronic address: karolina.kublickiene@ki.se.
D000368:Aged; D001158:Arteries / Q000503:physiopathology; D016022:Case-Control Studies; D004730:Endothelium, Vascular / Q000187:drug effects*; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000187:drug effects / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D008875:Middle Aged; D009203:Myocardial Infarction; D010636:Phenols; D048789:Phytoestrogens / Q000494:pharmacology*; D017698:Postmenopause; D011720:Pyrazoles / Q000494:pharmacology; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology; D050507:Subcutaneous Fat, Abdominal / Q000098:blood supply; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D010636:Phenols; D048789:Phytoestrogens; D011720:Pyrazoles; D013267:Stilbenes; D014665:Vasodilator Agents; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol; D004958:Estradiol; D019833:Genistein; D000077185:Resveratrol