Differential expression of capillary VEGF isoforms following traumatic brain injury

Dore‐Duffy, Paula; Wang, Xueqain; Mehedi, Afroza; Kreipke, Christian W.; Rafols, José A.

doi:10.1179/016164107x204729

Cited by 54 publications

(34 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Previously, we have shown that pericytes are highly responsive to low O 2 levels [10, 22, 27]. As early as one hour following exposure to low O 2, pericytes undergo changes in eicosanoid repertoire [22] and mount a HIF-1 response [22].…”

Section: Resultsmentioning

confidence: 99%

“…VEGF directly induces the proliferation and migration of pericytes under hypoxic conditions and also indirectly regulates pericyte recruitment via endothelial cell production of nitric oxide (NO) [46]. Pericytes constitutively express VEGF mRNA but transcripts are not translated until after the hypoxic stimulus [10, 27]. For this gene, a group of candidate regulatory microRNAs have been identified recently in tumor cells [12, 52] and human monocytes [53, 54].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Hypoxia Alters MicroRNA Expression in Rat Cortical Pericytes

Truettner¹,

Katyshev²,

Esen-Bilgin³

et al. 2013

MIRNA

Self Cite

View full text Add to dashboard Cite

Microvascular adaptation to metabolic stress is important in the maintenance of tissue homeostasis. Nowhere is this more important than in the central nervous system (CNS) where the cellular constituents of the neurovascularture including endothelial cells, pericytes and some astroglia must make fine-tuned autoregulatory modulations that maintain the delicate balance between oxygen availability and metabolic demand. miRNAs have been reported to play an important regulatory role in many cellular functions including cell differentiation, growth and proliferation, lineage determination, and metabolism. In this study, we investigated the possible role of miRNAs in the CNS capillary pericyte response to hypoxic stress. Micro-array analysis was used to examine the expression of 388 rat miRNAs in primary rat cortical pericytes with and without exposure to low oxygen (1%) after 24 or 48 hr. Pericytes subjected to hypoxia showed 27 miRNAs that were higher than control and 31 that were lower. Validation and quantification was performed by Real Time RT-PCR on pericytes subjected to 2 hr, 24 hr, or 48 hr of hypoxia. Hypoxia induced changes included physiological pathways governing the stress response, angiogenesis, migration and cell cycle regulation. miRNAs associated with HIF-1α (miR−322[1], miR−199a [2]), TGF-β1 (miR−140[3], miR−145[4], miR−376b−3p[5]) and VEGF (miR−126a[6], miR−297[7], miR−16[8], miR−17−5p[9]) were differentially regulated. Systematic and integrative analysis of possible gene targets analyzed by DAVID bioinformatics resource (http://david.abcc.ncifcrf.gov) and MetaSearch 2.0 (GeneGo) for some of these miRNAs was conducted to determine possible gene targets and pathways that may be affected by the post-transcriptional changes after hypoxic insult.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Hypoxia Alters MicroRNA Expression in Rat Cortical Pericytes

Truettner¹,

Katyshev²,

Esen-Bilgin³

et al. 2013

MIRNA

Self Cite

View full text Add to dashboard Cite

show abstract

“…In vivo studies in cats have shown that brain pericytes migrate away from capillaries rapidly following a hypoxic insult 120 and pericyte-endothelial cell ratio in brain is reduced one week following hypobaric hypoxia in rodents 121 . During hypoxia, VEGF levels are upregulated in pericytes within 24 hours and upregulated in astrocytes after 4 days 121 .…”

Section: Pericyte-endothelial Signal Transductionmentioning

confidence: 99%

“…During hypoxia, VEGF levels are upregulated in pericytes within 24 hours and upregulated in astrocytes after 4 days 121 . Inhibiting VEGF in chronic mild hypoxia (1% O 2 ) promotes angiopoietin-1 (Ang1)-mediated endothelial cell tight junction stabilization, whereas severe hypoxia (0.1% O 2 ) promotes apoptosis of endothelial cells, as shown in in vitro endothelial and pericyte co-cultures 122 .…”

Section: Pericyte-endothelial Signal Transductionmentioning

confidence: 99%

Pericytes of the neurovascular unit: key functions and signaling pathways

Ayyadurai²,

2016

View full text Add to dashboard Cite

Pericytes are vascular mural cells embedded in the basement membrane of blood microvessels. They extend their processes along capillaries, pre-capillary arterioles, and post-capillary venules. The central nervous system (CNS) pericytes are uniquely positioned within the neurovascular unit between endothelial cells, astrocytes, and neurons. They integrate, coordinate, and process signals from their neighboring cells to generate diverse functional responses that are critical for CNS functions in health and disease including regulation of the blood-brain barrier permeability, angiogenesis, clearance of toxic metabolites, capillary hemodynamic responses, neuroinflammation, and stem cell activity. Here, we examine the key signaling pathways between pericytes and their neighboring endothelial cells, astrocytes, and neurons that control neurovascular functions. We also review the role of pericytes in different CNS disorders including rare monogenic diseases and complex neurological disorders such as Alzheimer's disease and brain tumors. Finally, we discuss directions for future studies.

show abstract

“…VEGF is expressed in the CNS after experimental trauma and stroke [134,135,136] and has important implications in mediating ectopic migration of SVZ neuroblasts to the site of injury. Wang et al [137] showed that VEGF-overexpressing mice had enhanced SVZ cell proliferation after permanent focal cerebral ischemia, with chains of migratory neuroblasts extending from the SVZ to the peri-infarct cortex, leading to an ultimate increase in the number of newly generated cortical neurons at 14–28 days.…”

Section: Injury-induced Factors Mediating Redirected Migration To Dammentioning

confidence: 99%