ArticleAmerican journal of physiology. Regulatory, integrative and comparative physiology2010
Roles of CYP2C29 and RXR gamma in vascular EET synthesis of female mice.
Article in American journal of physiology. Regulatory, integrative and comparative physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 22 citations in OpenAlex.
- Transcriptome analysis of five-toed jerboa organs reveals high-altitude adaptation mechanisms.BMC genomics · 2025Article
- 1-methylnicotinamide modulates IL-10 secretion and voriconazole metabolism.Frontiers in immunology · 2025Article
- DEAD-Box Helicase 17 exacerbates non-alcoholic steatohepatitis via transcriptional repression of cyp2c29, inducing hepatic lipid metabolism disorder and eliciting the activation of M1 macrophages.Clinical and translational medicine · 2024Article
- Review
- Time serial transcriptome revealsCancer biology & medicine · 2020Article
- Sexually Dimorphic Regulation of EET Synthesis and Metabolism: Roles of Estrogen.Frontiers in pharmacology · 2018Article
- Sex-dependent alteration of cardiac cytochrome P450 gene expression by doxorubicin in C57Bl/6 mice.Biology of sex differences · 2017Article
- Cyp2c44 gene disruption exacerbated pulmonary hypertension and heart failure in female but not male mice.Pulmonary circulation · 2016Article
- EETs Elicit Direct Increases in Pulmonary Arterial Pressure in Mice.American journal of hypertension · 2016Article
- EET-dependent potentiation of pulmonary arterial pressure: sex-different regulation of soluble epoxide hydrolase.American journal of physiology. Lung cellular and molecular physiology · 2015Article
- Sexually dimorphic phenotype of arteriolar responsiveness to shear stress in soluble epoxide hydrolase-knockout mice.American journal of physiology. Heart and circulatory physiology · 2015Article
- Inhibition of soluble epoxide hydrolase increases coronary perfusion in mice.Physiological reports · 2015Article
- Soluble epoxide hydrolase-dependent regulation of myogenic response and blood pressure.American journal of physiology. Heart and circulatory physiology · 2014Article
- CYP2C29 produces superoxide in response to shear stress.Microcirculation (New York, N.Y. : 1994) · 2012Article
- Epoxides and soluble epoxide hydrolase in cardiovascular physiology.Physiological reviews · 2012Review
- A novel vascular EET synthase: role of CYP2C7.American journal of physiology. Regulatory, integrative and comparative physiology · 2011Article
- Estrogens and selective estrogen receptor modulators regulate gene and protein expression in the mesenteric arteries.Vascular pharmacologyArticle
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
We aimed to identify which cytochrome P-450 (CYP) family/subfamily, as well as related transcription factor(s), is responsible for the estrogen-dependent synthesis of epoxyeicosatrienoic acids (EETs) to initiate shear stress-induced vasodilation. Microarray analysis indicated a significant upregulation of CYP2C29 and retinoid X receptor gamma (RXRgamma) in isolated mesenteric arteries/arterioles of female endothelial nitric oxide synthase-knockout mice, a result that was validated by real-time RT-PCR. The cannulated vessels were then perfused with 2 and 10 dyn/cm(2) shear stress, followed by collection of the perfusate to determine EET concentrations and isoforms. Shear stress dose-dependently stimulated the release of EETs into the perfusate, associated with an EET-mediated vasodilation, in which predominantly 14,15-EET and 11,12-EET contributed to the responses ( approximately 87.4% of total EETs). Transfection of vessels with CYP2C29 siRNA eliminated the release of EETs into the perfusate, which was evidenced by an abolished vasodilation, and confirmed by RT-PCR and Western blot analyses. Knockdown of RXRgamma in these vessels significantly inhibited the production of EETs, parallel to a reduced vasodilation. RXRgamma siRNA not only silenced the vascular RXRgamma expression, but synchronously downregulated CYP2C29 expression, leading to a reduced EET synthesis. In conclusion, our data provide the first evidence for a specific signaling cascade, by which estrogen potentially activates the CYP2C29 gene in the absence of nitric oxide, to synthesize EETs in response to shear stress, via an RXRgamma-related regulatory mechanism.
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