Estrogen Treatment Inhibits Vascular Endothelial Senescence and Asymmetrical Dimethylarginine in Ovariectomized Rabbits

Abstract

To investigate the effects of estrogen treatment on aortic endothelial senescence and atherosclerosis, an ovariectomized female rabbit model was constructed, and human umbilical vein endothelial cells were utilized to explore the potential mechanisms. Twenty-eight female rabbits were randomized into 4 groups (7 each): sham operation, ovariectomized, ovariectomized plus low-dose estradiol treatment, and ovariectomized plus high-dose estradiol treatment. All rabbits were fed on high-cholesterol diet for 12 weeks. Blood samples were collected to determine the serum estradiol, asymmetric dimethyl L-arginine (ADMA), and lipid levels, and the aortas were separated for histopathologic analysis. After ovariectomy and high-fat diet, the concentration of serum estradiols declined significantly (P < 0.01) and the levels of ADMA and serum lipids increased (all P < 0.01) as the area of senescent endothelium and atherosclerotic lesions enlarged (both P < 0.01). However, administration of estradiols reduced the levels of ADMA, total cholesterol, and low-density lipoprotein (LDL) cholesterol and inhibited endothelial senescence and atherosclerosis (all P < 0.01). Simultaneously, the concentration of high-density lipoprotein cholesterol and triglyceride increased (all P < 0.01). In vitro experiments also confirmed that estradiols could decrease the ADMA levels induced by oxidized LDL and inhibited oxidized LDL–induced and ADMA-induced human umbilical vein endothelial cell senescence. These results indicate that estrogens can inhibit endothelial senescence and atherosclerosis with reduced ADMA levels and improved lipid profile.

Ethanolic extract of rhizome of Ligusticum chuanxiong Hort. (chuanxiong) enhances endothelium-dependent vascular reactivity in ovariectomized rats fed with high-fat diet

“…43,44 Hormone therapy in postmenopausal women (or OVX animal) could limit the uptake of cholesterol ester into the arterial wall, reduce oxidative stress, improve NO-mediated endothelium-dependent vasodilation and exert cardiovascular protection. 6,45,46 In the present study, ovariectomy plus HFD reduced the vasorelaxation induced by ACh (endothelium-dependent relaxation) without affecting that induced by SNP (endothelium-independent relaxation), suggesting LCEE could protect the endothelium from the detrimental effect of ovariectomy plus HFD. It was found that there was a partial loss of endothelial function in the aorta from the Control group rats since the maximum relaxation with ACh is around 60% of the contraction induced by phenylephrine (1 mM) (Fig.…”

Endothelium-dependent hyperpolarization: age, gender and blood pressure, do they matter?

“…17 β ‐Estradiol also upregulates the expression of SIRT1; this effect may contribute to the reduced senescence development and endothelial dysfunction in blood vessels of ovariectomized animals with 17 β ‐estradiol administration (Liao et al . , Bendale et al . ).…”

Effects of Estrogen and Folic Acid on High Fat Induced Hypercholesterolemic Mice

“…Estrogens improve glucose tolerance and responsiveness to insulin in part through direct effects on insulin receptor levels in adipocytes in rat [25]. Feeding mice with estradiols reduced the levels of total cholesterol, and low-density lipoprotein (LDL) cholesterol [26].…”