4.7 Review

Conflicting Roles of 20-HETE in Hypertension and Stroke

Journal

Publisher

MDPI
DOI: 10.3390/ijms20184500

Keywords

cytochrome P450; hypertension; stroke; cerebral autoregulation; endothelial dysfunction; vascular remodeling; vascular inflammation; blood-brain barrier; angiogenesis

Funding

  1. National Institutes of Health [AG050049, AG057842, P20GM104357, DK104184, HL138685]
  2. American Heart Association [16GRNT31200036]

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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.

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