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Upregulation of CYP1A1 and CYP1B1 in HUVEC by shear stress mediates downstream gene expression changes
Author(s) -
Conway Daniel E,
Sakurai Yumiko,
Eskin Suzanne G,
McIntire Larry V
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a186-c
Subject(s) - gene knockdown , downregulation and upregulation , cyp1b1 , umbilical vein , gene expression , chemistry , shear stress , microbiology and biotechnology , cytochrome p450 , biology , gene , biochemistry , enzyme , in vitro , materials science , composite material
CYP1A1 and CYP1B1 gene expression is dramatically upregulated by shear stress in human umbilical vein endothelial cells (HUVEC). CYP1A1 and 1B1 are capable of metabolizing arachidonic acid into epoxyeicosatrienoic acids (EETs). EETs are increased by shear stress in endothelial cells and mediate changes in gene transcription. We hypothesize that the increase in CYP1A1 or 1B1 regulates the expression of other shear stress responsive genes. We sought to determine whether protein levels of CYP1A1 and 1B1 are also increased by shear stress, examine the effect of siRNA knockdown of CYP1A1 or 1B1 on endothelin‐1 (ET‐1) expression, and determine if CYP1A1 and 1B1 are expressed in human arteries. HUVEC (P3‐5) were exposed to arterial levels of shear stress (25 dynes/cm2) for 24 hours. Densitometry of Western blots showed CYP1B1 protein significantly upregulated by flow. ET‐1 is a potent vasoconstrictor which is downregulated by shear stress. siRNA knockdown of CYP1B1 resulted in a 2.7 fold increase in ET‐1 mRNA, suggesting that a 1B1 metabolite mediates the shear stress down regulation of ET‐1. CYP1A1 and 1B1 protein was observed in the endothelium of human coronary arteries. Although CYP1A1 and 1B1 are thought to be important in response to environmental toxins, these data suggest these genes have an important physiological function in the response of endothelial cells to mechanical forces. [HL18672]