Estrogens and selective estrogen receptor modulators regulate gene and protein expression in the mesenteric arteries

Mark-Kappeler, Connie J.; Martin, Douglas; Eyster, Kathleen M.

doi:10.1016/j.vph.2011.05.002

Cited by 8 publications

(5 citation statements)

References 57 publications

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“…Interestingly, sEH is upregulated in the mesenteric arteries of these rats (Zhao et al, 2005). Treatment with ethinyl estradiol, tamoxifen, and raloxifene in ovariectomized rats upregulates sEH mRNA expression in mesenteric arteries (Mark-Kappeler et al, 2011). sEH protein is expressed in red blood cells (Jiang et al, 2008).…”

Section: Mammalian Gene Expressionmentioning

confidence: 99%

Soluble epoxide hydrolase: Gene structure, expression and deletion

Harris

Hammock

2013

Gene

192

184

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Mammalian soluble epoxide hydrolase (sEH) converts epoxides to their corresponding diols through the addition of a water molecule. sEH readily hydrolyzes lipid signaling molecules, including the epoxyeicosatrienoic acids (EETs), epoxidized lipids produced from arachidonic acid by the action of cytochrome p450s. Through its metabolism of the EETs and other lipid mediators, sEH contributes to the regulation of vascular tone, nociception, angiogenesis and the inflammatory response. Because of its central physiological role in disease states such as cardiac hypertrophy, diabetes, hypertension, and pain sEH is being investigated as a therapeutic target. This review begins with a brief introduction to sEH protein structure and function. sEH evolution and gene structure are then discussed before human small nucleotide polymorphisms and mammalian gene expression are described in the context of several disease models. The review ends with an overview of studies that have employed the sEH knockout mouse model.

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Section: Mammalian Gene Expressionmentioning

confidence: 99%

Soluble epoxide hydrolase: Gene structure, expression and deletion

Harris

Hammock

2013

Gene

192

184

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“…; Mark‐Kappeler et al. ; Harris and Hammock ). Therefore, sEH is a susceptible gene for hypertension‐associated cardiovascular diseases (Kersten et al.…”

Section: Introductionmentioning

confidence: 99%

Sexually dimorphic adaptation of cardiac function: roles of epoxyeicosatrienoic acid and peroxisome proliferator-activated receptors

Qin

Froogh

et al. 2016

Physiol Rep

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Epoxyeicosatrienoic acids (EETs) are cardioprotective mediators metabolized by soluble epoxide hydrolase (sEH) to form corresponding diols (DHETs). As a sex‐susceptible target, sEH is involved in the sexually dimorphic regulation of cardiovascular function. Thus, we hypothesized that the female sex favors EET‐mediated potentiation of cardiac function via downregulation of sEH expression, followed by upregulation of peroxisome proliferator‐activated receptors (PPARs). Hearts were isolated from male (M) and female (F) wild‐type (WT) and sEH‐KO mice, and perfused with constant flow at different preloads. Basal coronary flow required to maintain the perfusion pressure at 100 mmHg was significantly greater in females than males, and sEH‐KO than WT mice. All hearts displayed a dose‐dependent decrease in coronary resistance and increase in cardiac contractility, represented as developed tension in response to increases in preload. These responses were also significantly greater in females than males, and sEH‐KO than WT. 14,15‐EEZE abolished the sex‐induced (F vs. M) and transgenic model‐dependent (KO vs. WT) differences in the cardiac contractility, confirming an EET‐driven response. Compared with M‐WT controls, F‐WT hearts expressed downregulation of sEH, associated with increased EETs and reduced DHETs, a pattern comparable to that observed in sEH‐KO hearts. Coincidentally, F‐WT and sEH‐KO hearts exhibited increased PPAR α expression, but comparable expression of eNOS, PPAR β, and EET synthases. In conclusion, female‐specific downregulation of sEH initiates an EET‐dependent adaptation of cardiac function, characterized by increased coronary flow via reduction in vascular resistance, and promotion of cardiac contractility, a response that could be further intensified by PPAR α.

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“…47 In this context, up-regulation of SFRP2 and SFRP4 may mediate protective effects of estradiol on the arteries. On the other hand, we have observed a down-regulation of SFRP4 in response to ethinyl estradiol and equilin in the rat mesenteric arteries, 39 in a different species, a different vascular bed, and in the absence of atherosclerosis. In contrast, LRP6 is a co-receptor for frizzled.…”

Section: Discussionmentioning

confidence: 60%

“…38 In contrast to the current data, we have shown that IGF-1 decreased in the rat mesenteric arteries in response to ethinyl estradiol. 39 Similarly, Scheidegger and coworkers 40 showed that estrogen caused a decrease in IGF-1 expression in aortic smooth muscle cells. These data thus indicate a pleiotropic effect of estrogen on IGF-1 in the vasculature.…”

Section: Discussionmentioning

confidence: 96%

Effects of estradiol on transcriptional profiles in atherosclerotic iliac arteries in ovariectomized cynomolgus macaques

et al. 2014

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Objective To assess the in vivo effects of estradiol treatment on arterial gene expression in atherosclerotic post-menopausal female monkeys. Methods Eight ovariectomized cynomolgus monkeys were fed atherogenic diets for 6.5 years. The left iliac artery was biopsied before randomization to estradiol (E2, 1 mg/day human equivalent dose, n=4) or vehicle (n=4) groups for 8 months. The right iliac artery was obtained at necropsy. Transcriptional profiles in pretreatment versus posttreatment iliac arteries were compared to assess responses of atherosclerotic arteries to estradiol. Results Iliac artery plaque size did not differ between E2 and placebo groups at baseline or over the treatment period. Nevertheless, estradiol treatment was associated with increased expression of 106 genes and decreased expression of 26 genes in iliac arteries. Estradiol treatment increased expression of extracellular matrix (ECM) genes, including types I and VI collagen (COL1A1, COL6A2) and fibulin-2 (FBLN-2), suggestive of an increase in the proportion or phenotype of smooth muscle or fibroblasts in the lesions. Also increased were components of the insulin-like growth factor (IGF) pathway [IGF-1, IGF binding protein 4 (IGFBP4) and IGFBP5], and the Wnt signaling pathway [secreted frizzled-related protein 2 (SFRP2), SFRP4, low density lipoprotein receptor-related protein 6 (LRP6), and Wnt 1 inducible signaling pathway protein 2 (WISP2)]. Conclusions Estradiol treatment of monkeys with established atherosclerosis resulted in effects on iliac artery gene expression that suggested changes in the cellular composition of the lesions. Moreover, it is likely that the presence of atherosclerotic plaque affected the gene expression responses of the arteries to estrogen.

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Estrogens and selective estrogen receptor modulators regulate gene and protein expression in the mesenteric arteries

Cited by 8 publications

References 57 publications

Soluble epoxide hydrolase: Gene structure, expression and deletion

Soluble epoxide hydrolase: Gene structure, expression and deletion

Sexually dimorphic adaptation of cardiac function: roles of epoxyeicosatrienoic acid and peroxisome proliferator-activated receptors

Effects of estradiol on transcriptional profiles in atherosclerotic iliac arteries in ovariectomized cynomolgus macaques

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