Conflicting Roles of 20-HETE in Hypertension and Stroke

Shekhar, Shashank; Varghese, Kevin; Li, Man; Fan, Letao; Booz, George W.; Roman, Richard J.; Fan, Fan

doi:10.3390/ijms20184500

Cited by 33 publications

(23 citation statements)

References 82 publications

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“…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 ).…”

Section: Introductionmentioning

confidence: 99%

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

Wang

Zhang

Liu

et al. 2020

American Journal of Physiology-Heart and Circulatory Physiology

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Using perfusion fixation of the middle cerebral artery (MCA) in calcium-free solution at physiological pressure and systematically randomly sampling the sections prepared from the same M2 segments of MCA, we found that there are structural differences that are associated with altered cerebral blood flow (CBF) autoregulation but not neurovascular coupling and cognition in young, healthy Sprague-Dawley (SD) rats. Understanding the intrinsic differences in cerebrovascular structure and function in males and females is essential to develop new pharmaceutical treatments for cerebrovascular disease (CVD).

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Section: Introductionmentioning

confidence: 99%

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

Wang

Zhang

Liu

et al. 2020

American Journal of Physiology-Heart and Circulatory Physiology

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“…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).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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20-HETE is a potent vasoconstrictor that is implicated in the regulation of blood pressure, cerebral blood flow and neuronal death following ischemia. Numerous human genetic studies have shown that inactivating variants in the cytochrome P450 enzymes that produce 20-HETE are associated with hypertension, stroke and cerebrovascular disease. However, little is known about the expression and cellular distribution of the cytochrome P450A enzymes (CYP4A) that produce 20-HETE or the newly discovered 20-HETE receptor (GPR75) in the brain. The present study examined the cell types and regions in the rat forebrain that express CYP4A and GPR75. Brain tissue slices from Sprague Dawley (SD), Dahl Salt-Sensitive (SS) and CYP4A1 transgenic rat strains, as well as cultured human cerebral pericytes and cerebral vascular smooth muscle cells, were analyzed by fluorescent immunostaining. Tissue homogenates from these strains and cultured cells were examined by Western blot. In the cerebral vasculature, CYP4A and GPR75 were expressed in endothelial cells, vascular smooth muscle cells and the glial limiting membrane of pial arteries and penetrating arterioles but not in the endothelium of capillaries. CYP4A, but not GPR75, was expressed in astrocytes. CYP4A and GPR75 were both expressed in a subpopulation of pericytes on capillaries. The diameters of capillaries were significantly decreased at the sites of first and second-order pericytes that expressed CYP4A. Capillary diameters were unaffected at the sites of other pericytes that did not express CYP4A. These findings implicate 20-HETE as a paracrine mediator in various components of the neurovascular unit and are consistent with 20-HETE's emerging role in the regulation of cerebral blood flow, blood-brain barrier integrity, the pathogenesis of stroke and the vascular contributions to cognitive impairment and dementia. Moreover, this study highlights GPR75 as a potential therapeutic target for the treatment of these devastating conditions.

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“…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).…”

Section: Resultsmentioning

confidence: 99%