TY - JOUR
T1 - Conflicting roles of 20-HETE in hypertension and stroke
AU - Shekhar, Shashank
AU - Varghese, Kevin
AU - Li, Man
AU - Fan, Letao
AU - Booz, George W.
AU - Roman, Richard J.
AU - Fan, Fan
N1 - Funding Information:
Funding: This work was supported by the National Institutes of Health (AG050049, AG057842, P20GM104357, DK104184, and HL138685) and the American Heart Association (16GRNT31200036).
Publisher Copyright:
© 2019, MDPI AG. All rights reserved.
PY - 2019/9/2
Y1 - 2019/9/2
N2 - Hypertension is the most common modifiable risk factor for stroke, and understanding the underlying mechanisms of hypertension and hypertension-related stroke is crucial. 20-hydroxy-5, 8, 11, 14-eicosatetraenoic acid (20-HETE), which plays an important role in vasoconstriction, autoregulation, endothelial dysfunction, angiogenesis, inflammation, and blood-brain barrier integrity, has been linked to hypertension and stroke. 20-HETE can promote hypertension by potentiating the vascular response to vasoconstrictors; it also can reduce blood pressure by inhibition of sodium transport in the kidney. The production of 20-HETE is elevated after the onset of both ischemic and hemorrhagic strokes; on the other hand, subjects with genetic variants in CYP4F2 and CYP4A11 that reduce 20-HETE production are more susceptible to stroke. This review summarizes recent genetic variants in CYP4F2, and CYP4A11 influencing 20-HETE production and discusses the role of 20-HETE in hypertension and the susceptibility to the onset, progression, and prognosis of ischemic and hemorrhagic strokes.
AB - Hypertension is the most common modifiable risk factor for stroke, and understanding the underlying mechanisms of hypertension and hypertension-related stroke is crucial. 20-hydroxy-5, 8, 11, 14-eicosatetraenoic acid (20-HETE), which plays an important role in vasoconstriction, autoregulation, endothelial dysfunction, angiogenesis, inflammation, and blood-brain barrier integrity, has been linked to hypertension and stroke. 20-HETE can promote hypertension by potentiating the vascular response to vasoconstrictors; it also can reduce blood pressure by inhibition of sodium transport in the kidney. The production of 20-HETE is elevated after the onset of both ischemic and hemorrhagic strokes; on the other hand, subjects with genetic variants in CYP4F2 and CYP4A11 that reduce 20-HETE production are more susceptible to stroke. This review summarizes recent genetic variants in CYP4F2, and CYP4A11 influencing 20-HETE production and discusses the role of 20-HETE in hypertension and the susceptibility to the onset, progression, and prognosis of ischemic and hemorrhagic strokes.
KW - Angiogenesis
KW - Blood-brain barrier
KW - Cerebral autoregulation
KW - Cytochrome P450
KW - Endothelial dysfunction
KW - Hypertension
KW - Stroke
KW - Vascular inflammation
KW - Vascular remodeling
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U2 - 10.3390/ijms20184500
DO - 10.3390/ijms20184500
M3 - Review article
C2 - 31514409
AN - SCOPUS:85072144454
SN - 1661-6596
VL - 20
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 18
M1 - 4500
ER -