Short-term transdermal estradiol enhances nitric oxide synthase III and estrogen receptor mRNA expression in arteries of women with coronary artery disease

Objective To analyze the short-term effects of estradiol (E2) on the expression of nitric oxide synthase (NOS III) and estrogen receptors (ER) α and β. Methods We studied 20 post-menopausal women with coronary artery disease (CAD) undergoing CABG surgery with left internal mammary artery (LIMA) grafting. Ten women received treatment with transdermal E2 prior to surgery (48–72 h) and 10 did not. The distal segment of the LIMA was excised and processed to determine mRNA expression of NOS III and ER α and β (RT-PCR). Expression of NOS III and ER α and β was measured in arbitrary densitometric units (ADUs) relative to GPdH expression, constitutively expressed in human vessels. Results NOS III and ER α and β mRNA expression was enhanced in women treated with E2 as compared to the control group (NOS III: 1.69±0.61 versus 1.14±0.48 ADUs, p=0.04; ER α: 6.52±6.80 versus 1.83±1.22 ADUs, p=0.04; ER β: 4.20±3.42 versus 1.56±0.59 ADUs, p=0.03). ER α, but not ER β expression, correlated with NOS III expression (r=0.70, p<0.001). Conclusions After treatment with E2, NOS III, ER α, and ER β mRNA expression was enhanced in arterial vessels of postmenopausal women with CAD. NOS III mRNA expression was only correlated to ER α expression, suggesting that NOS III activation could be more mediated by ER α.