Pericytes in Cerebrovascular Diseases: An Emerging Therapeutic Target

Su, Xiaojuan; Huang, Lingyi; Qu, Yi; Xiao, Dongqiong; Mu, Dezhi

doi:10.3389/fncel.2019.00519

Cited by 32 publications

(24 citation statements)

References 122 publications

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“…Targeting pericytes in cerebrovascular disease is an emerging area of research (59). In disease states such as ischemic stroke, an abundant release of arachidonic acid, the substrate for 20-HETE production, is observed due to cell death.…”

Section: -Hete and Cerebral Blood Flowmentioning

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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Section: -Hete and Cerebral Blood Flowmentioning

confidence: 99%

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

et al. 2020

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“…This was demonstrated by genetic ablation of pericytes resulting in loss of pleiotrophin (PTN) expression; PTN is a pericyte-secreted growth factor and loss of this factor contributed to neuronal death in this study (Nikolakopoulou et al, 2019). Hence, pericytes can play a detrimental role in ischemia-reperfusion injury and thus represent a promising therapeutic target, as reviewed elsewhere (Cai et al, 2017;Su et al, 2019;Uemura et al, 2020).…”

Section: Effects Of Stroke On Pericyte Functionmentioning

confidence: 70%

“…Following stroke, pericytes play a role in BBB remodeling and vessel stability (Su et al, 2019). Pericytes were shown to migrate away from brain microvessels in the first 2 h after occlusion of the internal carotid artery in cats (Gonul et al, 2002).…”

Section: Effects Of Stroke On Pericyte Structurementioning

confidence: 99%

Structural and Functional Remodeling of the Brain Vasculature Following Stroke

2020

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“…Moreover, pericytes play a major role in the differentiation of ECs during fetal life, even before the appearance of astrocytes [40]. The recruitment of pericytes to endothelium and the interaction between the two are essential factors for the formation, maturation, and maintenance of the BBB [40][41][42].…”

Section: Blood-brain Barriermentioning

confidence: 99%

Involvement of Testosterone Signaling in the Integrity of the Neurovascular Unit in the Male: Review of Evidence, Contradictions, and Hypothesis

Ahmadpour

Grange-Messent²

2020

Neuroendocrinology

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Age-related central nervous system function decline and increased susceptibility of females compared to males with respect to prevalence of several neurodegenerative and neuropsychiatric diseases are both based on the principle that hormonal factors could be involved. These cerebral disorders are characterized by an alteration of blood-brain barrier (BBB) properties and chronic neuroinflammation, which lead to disease progression. Neuroinflammation, in turn, contributes to BBB dysfunction. The BBB and its environment, called the neurovascular unit (NVU), are crucial for cerebral homeostasis and neuronal function. Interestingly, sex steroids influence BBB properties and modulate neuroinflammatory responses. To date however, the majority of work reported has focused on the effects of estrogens on BBB function and neuroinflammation in female mammals. In contrast, the effects of testosterone signaling on the NVU in males are still poorly studied. The aim of this review was to summarize and discuss the literature, providing insights and contradictions to highlight hypothesis and the need for further investigations.

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Pericytes in Cerebrovascular Diseases: An Emerging Therapeutic Target

Cited by 32 publications

References 122 publications

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

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

Structural and Functional Remodeling of the Brain Vasculature Following Stroke

Involvement of Testosterone Signaling in the Integrity of the Neurovascular Unit in the Male: Review of Evidence, Contradictions, and Hypothesis

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