2009
DOI: 10.1038/ki.2009.67
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Overexpression of cytochrome P450 4F2 in mice increases 20-hydroxyeicosatetraenoic acid production and arterial blood pressure

Abstract: Cytochrome P450 4F2 (CYP4F2) activity is thought to be a factor in the pathogenesis of hypertension through its bioactive metabolite 20-hydroxyeicosatetraenoic acid (20-HETE). We previously found that a gain-in-function CYP4F2 variant in a Chinese cohort was associated with elevated urinary 20-HETE and hypertension. To further explore this association we generated a transgenic mouse model expressing CYP4F2 driven by a modified mouse kidney androgen-regulated protein promoter. This heterologous promoter regulat… Show more

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Cited by 42 publications
(47 citation statements)
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“…The hepatic and renal microsomes were prepared according to the method described previously (12). The conversion of AA was assessed in a reaction mixture of 100 mM potassium phosphate buffer (pH 7.4) containing 3.3 mM MgCl 2 , 80 µM AA (Cayman Chemical Company), 1 mM NADPH (Roche Applied Science, Basel, Switzerland) and 0.6 µg/µl mouse renal microsomes.…”
Section: Aa Hydroxylation Assay Of Hepatic and Renal Microsomesmentioning
confidence: 99%
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“…The hepatic and renal microsomes were prepared according to the method described previously (12). The conversion of AA was assessed in a reaction mixture of 100 mM potassium phosphate buffer (pH 7.4) containing 3.3 mM MgCl 2 , 80 µM AA (Cayman Chemical Company), 1 mM NADPH (Roche Applied Science, Basel, Switzerland) and 0.6 µg/µl mouse renal microsomes.…”
Section: Aa Hydroxylation Assay Of Hepatic and Renal Microsomesmentioning
confidence: 99%
“…CYP4F2 transgenic mice from the FVB/N strain were generated and characterized as previously described (12). The mice were fed with standard mouse chow and water ad libitum, and bred in a 12:12 h light-dark cycle system at 23˚C.…”
Section: Methodsmentioning
confidence: 99%
“…The other is anti-hypertension caused by inhibition of sodium reabsorption (6,7). We have previously elucidated the prohypertensive action of 20-HETE derived from CYP4F2 in the human population and in a transgenic mouse model (8,9). We initially identified that a functional haplotype of CYP4F2 with increased transcriptional activity is associated with elevated urinary 20-HETE and hypertension in the Chinese population (8).…”
Section: Introductionmentioning
confidence: 99%
“…We initially identified that a functional haplotype of CYP4F2 with increased transcriptional activity is associated with elevated urinary 20-HETE and hypertension in the Chinese population (8). Then, we successfully generated CYP4F2 transgenic mice of the FVB/N strain with the kidney androgen-regulated protein (KAP) promoter (KAP-CYP4F2), and documented that the preferential renal overexpression of CYP4F2 enhances 20-HETE production and elevates systolic blood pressure (SBP) (9). Nevertheless, the following problems should be further addressed: i) whether or not the FVB/N genetic background is involved in the phenotype of the transgenic mice and ii) assessment of the phenotype of transgenic mice with strong CYP4F2 overexpression in multiple tissues and organs.…”
Section: Introductionmentioning
confidence: 99%
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