Vascular Endothelial Estrogen Receptor α Is Modulated by Estrogen Status and Related to Endothelial Function and Endothelial Nitric Oxide Synthase in Healthy Women

ABSTRACT Context and Objective Estrogen receptor α (ERα), a potent transcription factor expressed in vascular endothelial cells, plays a key role in regulating vascular function and health. We determined whether vascular endothelial cell expression of ERα is influenced by estrogen status and is related to vascular endothelial function in healthy women. Methods ERα protein expression was measured (quantitative immunofluorescence) in endothelial cells from peripheral veins of 16 healthy, premenopausal women during the early follicular (EF) and late follicular (LF) phases of the menstrual cycle and 17 estrogen-deficient postmenopausal women. Endothelial-dependent dilation (EDD; brachial artery flow-mediated dilation) and endothelial nitric oxide synthase (eNOS) expression and activation were also measured in a subgroup of women. Results In premenopausal women (n = 10), ERα expression was 30% lower (P < 0.001) during the EF (low estrogen) compared with the LF (high estrogen) phase of the menstrual cycle. In postmenopausal women, ERα expression was 33% lower (P < 0.001) compared with the LF phase of the menstrual cycle in premenopausal women. ERα expression was strongly related (r = 0.67; P < 0.001) to EDD, which was reduced in postmenopausal women. ERα abundance was positively related to expression of eNOS (r = 0.54; P = 0.009; n = 21) and ser1177 phosphorylated eNOS (r = 0.59; P = 0.006; n = 20). Conclusions These results provide the first evidence that expression of ERα in vascular endothelial cells is modulated by estrogen status and may be a key determinant of vascular endothelial function in healthy pre- and postmenopausal women. ERα expression may influence vascular endothelial function in women by affecting protein levels and activation of eNOS.

Download Full-text

Downregulated GTCPH I/BH4 Pathway and Decreased Function of Circulating Endothelial Progenitor Cells and Their Relationship with Endothelial Dysfunction in Overweight Postmenopausal Women

Stem Cells International ◽

10.1155/2018/4756263 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11 ◽

Cited By ~ 5

Author(s):

Ying Luo ◽

Zhenhua Huang ◽

Jinli Liao ◽

Zhihao Liu ◽

Xiaopeng Li ◽

...

Keyword(s):

Endothelial Function ◽

Postmenopausal Women ◽

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Premenopausal Women ◽

Endothelial Damage ◽

Normal Weight ◽

Vascular Endothelial ◽

Vascular Endothelial Function ◽

Endothelial Progenitor

Endothelial progenitor cells (EPCs) have endogenous endothelium-reparative potential, but obesity impairs EPCs. Overweight premenopausal women have a normal number of circulating EPCs with functional activity, but whether EPCs in overweight postmenopausal women can repair obesity-related endothelial damage requires further investigation. For this purpose, we examined the function and number of circulating EPCs, evaluated vascular endothelial function, and explored the underlying mechanism. Compared with normal weight or overweight age-matched men, postmenopausal women (overweight or normal weight) had a diminished number of circulating EPCs and impaired vascular endothelial function, as detected by flow-mediated dilatation. Moreover, GTCPH I expression and the nitric oxide level in overweight postmenopausal women and men were significantly decreased. Together, our findings demonstrate that the number or function of circulating EPCs and endothelial function, which is partially regulated by the GTCPH I/BH4 signaling pathway, is not preserved in overweight postmenopausal women. The GTCPH I/BH4 pathway in circulating EPCs may be a potential therapeutic target for endothelial injury in overweight postmenopausal women.

Download Full-text

Study on Damage Mechanism and Repair of Vascular Endothelial Cells Based on Ultrasound Technology

BioMed Research International ◽

10.1155/2021/6680356 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Shuhao Deng ◽

Quan Jiang ◽

Xin Lu ◽

Yuan Zhang

Keyword(s):

Endothelial Cells ◽

Endothelial Function ◽

Relaxation Function ◽

Vascular Endothelial Cells ◽

Early Stage ◽

Gradient Centrifugation ◽

Control Group ◽

Dependent Manner ◽

Vascular Endothelial ◽

Vascular Endothelial Function

Objective. To detect the endothelial function of external iliac artery in rats with different stages of atherosclerosis by high-resolution ultrasound, so as to provide experimental methodological basis for evaluating the function of vascular endothelial cells by ultrasound. Methods. The animals were randomly divided into the control group ( n = 6 ) and the atherosclerosis model group ( n = 15 ). The atherosclerosis group was further divided into 4-week group, 8-week group, and 12-week group, with 5 animals in each group. After separating and grinding rat spleen, the obtained cells were cultured by density gradient centrifugation. After the cells adhered, the morphology of the cells was observed under a microscope and identified by DiI-Ac-LDL and FITC-UEA-I double staining. The activities of LDH and SOD, the contents of MDA and GSH, and the contents of NO in plasma were detected by biochemical methods. Results. The protective effect of rosanilin on brain injury in rats with acute hypobaric hypoxia and its regulation on the expression of pAkt protein; ox-LDL inhibited the proliferation activity of EPCs in a concentration-dependent manner. The expression of KLF2 and S1PR1 in HAEC can be knocked down by small interfering RNA, and knocking down KLF2 can not only downregulate the expression of S1PR1 but also downregulate HAVEN. With the development of atherosclerosis, the endothelium-dependent relaxation function and endothelium-independent relaxation function of the control group and the atherosclerosis model at 4, 8, and 12 weeks were damaged in different degrees and gradually aggravated. Conclusion. Atherosclerosis is a disease with both morphological and functional damage, and vascular endothelial function is damaged in the early stage with corresponding pathological changes. Ultrasound is an effective method to evaluate vascular endothelial function.

Download Full-text

Thiazolidinediones Suppress Endothelin-1 Secretion from Bovine Vascular Endothelial Cells: A New Possible Role of PPARγ on Vascular Endothelial Function

Biochemical and Biophysical Research Communications ◽

10.1006/bbrc.1998.0126 ◽

1999 ◽

Vol 254 (3) ◽

pp. 757-763 ◽

Cited By ~ 140

Author(s):

Hiroaki Satoh ◽

Kazuhisa Tsukamoto ◽

Yoshiaki Hashimoto ◽

Naoaki Hashimoto ◽

Masako Togo ◽

...

Keyword(s):

Endothelial Cells ◽

Endothelial Function ◽

Vascular Endothelial Cells ◽

Vascular Endothelial ◽

Vascular Endothelial Function ◽

Endothelin 1

Download Full-text

Mitochondrial arginase II constrains endothelial NOS-3 activity

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00700.2007 ◽

2007 ◽

Vol 293 (6) ◽

pp. H3317-H3324 ◽

Cited By ~ 38

Author(s):

Hyun Kyo Lim ◽

Hyun Kyoung Lim ◽

Sungwoo Ryoo ◽

Alex Benjo ◽

Karl Shuleri ◽

...

Keyword(s):

Endothelial Cells ◽

Vascular Endothelial Cells ◽

Vascular Stiffness ◽

No Production ◽

Vascular Endothelial ◽

Vascular Endothelial Function ◽

Vasoconstrictor Response ◽

Arginase Ii ◽

Endothelial Nitric Oxide ◽

Arginase I

Emerging evidence supports the idea that arginase, expressed in the vascular endothelial cells of humans and other species, modulates endothelial nitric oxide (NO) synthase-3 (NOS-3) activity by regulating intracellular l-arginine bioavailability. Arginase II is thought to be expressed in the mitochondria of a variety of nonendothelial cells, whereas arginase I is known to be confined to the cytosol of hepatic and other cells. The isoforms that regulate NOS-3 and their subcellular distribution, however, remain incompletely characterized. We therefore tested the hypothesis that arginase II is confined to the mitochondria and that mitochondrial arginase II reciprocally regulates vascular endothelial NO production. Western blot analysis, immunocytochemistry with MitoTracker, and immunoelectron microscopy confirmed that arginase II is confined predominantly but not exclusively to the mitochondria. Arginase activity was significantly decreased, whereas NO production was significantly increased in the aorta and isolated endothelial cells from arginase II knockout (ArgII−/−) mice compared with wild-type (WT) mice. The vasorelaxation response to acetylcholine (ACh) was markedly enhanced and the vasoconstrictor response to phenylephrine (PE) attenuated in ArgII−/− in pressurized mouse carotid arteries. Furthermore, inhibition of NOS-3 by NG-nitro-l-arginine methyl ester (l-NAME) impaired ACh response and restored the PE response to that observed in WT vessels. Vascular stiffness, as assessed by pulse wave velocity (PWV), was significantly decreased in ArgII−/− compared with WT mice. On the other hand, 14 days of oral l-NAME treatment significantly increased PWV in both WT and ArgII−/− mice, such that they were not significantly different from one another. These data suggest that arginase II is predominantly confined to the mitochondria and that this mitochondrial arginase II regulates NO production, vascular endothelial function, and vascular stiffness by modulating NOS-3 activity.

Download Full-text