TY - JOUR
T1 - Effect of cytochrome P450 metabolites of arachidonic acid in nephrology
AU - Fan, Fan
AU - Roman, Richard J.
N1 - Funding Information:
This study was supported by grants AG050049 (to F.F.), P20GM104357 (pilot: to F.F.; cores B and C: to R.J.R.), HL36279 (to R.J.R.), and DK104184 (to R.J.R.) from the National Institutes of Health and grant 16GRNT31200036 (to F.F.) from the American Heart Association.
Publisher Copyright:
© 2017 by the American Society of Nephrology.
PY - 2017/10
Y1 - 2017/10
N2 - Thirty-five years ago, a third pathway for the metabolism of arachidonic acid by cytochrome P450 enzymes emerged. Subsequent work revealed that 20-hydroxyeicosatetraenoic and epoxyeicosatrienoic acids formed by these pathways have essential roles in the regulation of renal tubular and vascular function. Sequence variants in the genes that produce 20-hydroxyeicosatetraenoic acid are associated with hypertension in humans, whereas the evidence supporting a role for variants in the genes that alter levels of epoxyeicosatrienoic acids is less convincing. Studies in animal models suggest that changes in the production of cytochrome P450 eicosanoids alter BP. However, the mechanisms involved remain controversial, especially for 20-hydroxyeicosatetraenoic acid, which has both vasoconstrictive and natriuretic actions. Epoxyeicosatrienoic acids are vasodilators with anti-inflammatory properties that oppose the development of hypertension and CKD; 20-hydroxyeicosatetraenoic acid levels are elevated after renal ischemia and may protect against injury. Levels of this eicosanoid are also elevated in polycystic kidney disease and may contribute to cyst formation. Our review summarizes the emerging evidence that cytochrome P450 eicosanoids have a role in the pathogenesis of hypertension, polycystic kidney disease, AKI, and CKD.
AB - Thirty-five years ago, a third pathway for the metabolism of arachidonic acid by cytochrome P450 enzymes emerged. Subsequent work revealed that 20-hydroxyeicosatetraenoic and epoxyeicosatrienoic acids formed by these pathways have essential roles in the regulation of renal tubular and vascular function. Sequence variants in the genes that produce 20-hydroxyeicosatetraenoic acid are associated with hypertension in humans, whereas the evidence supporting a role for variants in the genes that alter levels of epoxyeicosatrienoic acids is less convincing. Studies in animal models suggest that changes in the production of cytochrome P450 eicosanoids alter BP. However, the mechanisms involved remain controversial, especially for 20-hydroxyeicosatetraenoic acid, which has both vasoconstrictive and natriuretic actions. Epoxyeicosatrienoic acids are vasodilators with anti-inflammatory properties that oppose the development of hypertension and CKD; 20-hydroxyeicosatetraenoic acid levels are elevated after renal ischemia and may protect against injury. Levels of this eicosanoid are also elevated in polycystic kidney disease and may contribute to cyst formation. Our review summarizes the emerging evidence that cytochrome P450 eicosanoids have a role in the pathogenesis of hypertension, polycystic kidney disease, AKI, and CKD.
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U2 - 10.1681/ASN.2017030252
DO - 10.1681/ASN.2017030252
M3 - Review article
C2 - 28701518
AN - SCOPUS:85030478376
SN - 1046-6673
VL - 28
SP - 2845
EP - 2855
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
IS - 10
ER -