Overexpression of cytochrome P450 4F2 in mice increases 20-hydroxyeicosatetraenoic acid production and arterial blood pressure

Kidney Int. 2009 Jun;75(12):1288-1296. doi: 10.1038/ki.2009.67. Epub 2009 Mar 11.


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 regulated the expression of luciferase and his-tagged CYP4F2 in transfected HEK 293 cells. In the kidney of transgenic mice, CYP4F2 was localized to renal proximal tubule epithelia and was expressed at a higher level than in control mice, leading to increased urinary 20-HETE excretion. Assessment of CYP4F2 activity by an arachidonic acid hydroxylation assay showed that 20-HETE production was significantly higher in kidney microsomes of transgenic mice compared to control mice, as was their systolic blood pressure. There was a positive correlation of blood pressure with urinary 20-HETE levels. Our results show that increased expression of CYP4F2 in mice enhanced 20-HETE production and elevated blood pressure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Blood Pressure / genetics
  • Blood Pressure / physiology
  • Cell Line
  • Cytochrome P-450 Enzyme System / genetics*
  • Cytochrome P-450 Enzyme System / metabolism*
  • Cytochrome P450 Family 4
  • DNA, Complementary / genetics
  • Disease Models, Animal
  • Gene Expression
  • Humans
  • Hydroxyeicosatetraenoic Acids / biosynthesis*
  • Hydroxyeicosatetraenoic Acids / urine
  • Hypertension / etiology*
  • Hypertension / genetics
  • Hypertension / physiopathology
  • Kidney Tubules, Proximal / metabolism
  • Mice
  • Mice, Transgenic
  • Promoter Regions, Genetic
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Transfection


  • DNA, Complementary
  • Hydroxyeicosatetraenoic Acids
  • Recombinant Proteins
  • 20-hydroxy-5,8,11,14-eicosatetraenoic acid
  • Cytochrome P-450 Enzyme System
  • Cytochrome P450 Family 4
  • CYP4F2 protein, human