Conflicting Roles of 20-HETE in Hypertension and Stroke

Abstract

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.

Sex differences in the structure and function of rat middle cerebral arteries

“…As the largest branch of the internal carotid artery, the MCA provides blood supply to the lateral convexity of the hemisphere, including frontal, parietal, temporal, and occipital lobes, as well as the lateral sulcus, insula cortex, lenticular nucleus, and internal capsule ( 52 , 85 ). Ischemic stroke comprises 85%, and 15% is hemorrhagic stroke ( 67 ). Embolism of the lenticulostriate branches of the MCA is the most common cause of ischemic stroke; ~33% of saccular aneurysms (the most common subtype of aneurysm) are found in the MCA, and aneurysm disruption is the most common cause of hemorrhagic stroke ( 52 ).…”

20-HETE Enzymes and Receptors in the Neurovascular Unit: Implications in Cerebrovascular Disease

“…Stroke and dementia are leading causes of serious-long term disability and mortality in the United States (1,2). These conditions share significant overlapping pathophysiology and associated risk factors (3).…”

20‐HETE synthesis inhibition attenuates traumatic brain injury–induced mitochondrial dysfunction and neuronal apoptosis via the SIRT1/PGC‐1α pathway: A translational study

“…To verify the changes in 20‐HETE levels after TBI, Western blotting was used to evaluate the possible changes in the levels of CYP4A, the 20‐HETE synthetase, 32 in the perilesional cortex. CYP4A level was increased at 6 hours and reached a peak at 24 hours (Figure 2A,B).…”