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Cerebral ischemia-induced angiogenesis is dependent on tumor necrosis factor receptor 1-mediated upregulation of α5β1 and αVβ3 integrins.
- Source :
-
Journal of Neuroinflammation . 9/1/2016, Vol. 13, p1-12. 12p. - Publication Year :
- 2016
-
Abstract
- <bold>Background: </bold>The pro-inflammatory cytokine, tumor necrosis factor-α (TNF-α), is expressed in ischemic tissue and is known to modulate angiogenesis; however, the role of the two distinct TNF-α receptors, TNFR1 and TNFR2, in mediating angiogenic signaling after cerebral ischemic stroke is relatively unknown.<bold>Methods: </bold>C57BL6 mice were subject to 90 min of ischemia by temporary occlusion of the middle cerebral artery (MCAO) and given daily intra-cerebroventricular injections of antibodies against TNFR1, TNFR2 or control IgG (doses of 10, 50, and 100 ng/day) for 4 days following 90 min MCAO. Vascular remodeling and α5β1 and αVβ3 integrin expression were then examined in the brains of these mice after 4, 7, and 14 days post-ischemia. In parallel in vitro studies, flow cytometry was used to determine the influence of TNF-α on proliferation and integrin expression of human brain microvascular endothelial cells (HBMECs).<bold>Results: </bold>The post-ischemic cerebral angiogenic response was inhibited by antibodies against TNFR1 but not TNFR2, and this correlated with reduced endothelial proliferation and decreased α5β1 and αVβ3 integrin expression after 4 and 7 days post-ischemia. Consistent with these findings, in vitro studies showed that TNF-α induced endothelial proliferation and upregulation of α5β1 and αVβ3 integrins was abrogated by anti-TNFR1 but not anti-TNFR2 antibodies in cultured HBMECs. In addition, blocking antibodies to α5β1 and αVβ3 integrins significantly inhibited TNF-α-induced HBMEC proliferation.<bold>Conclusions: </bold>Our results suggest that TNFR1-mediated signaling plays a critical role in triggering angiogenic integrins and subsequent angiogenic responses following cerebral ischemia. These novel findings could form a platform for future therapeutic strategies aimed at stimulating angiogenesis following cerebral ischemia. [ABSTRACT FROM AUTHOR]
- Subjects :
- *CEREBRAL ischemia
*NEOVASCULARIZATION
*STROKE patients
*INTEGRINS
*ANGIOGENIN
*ANIMAL experimentation
*BIOCHEMISTRY
*BIOLOGICAL models
*BRAIN
*CELL culture
*CELL physiology
*CELL receptors
*CELLULAR signal transduction
*CYTOKINES
*EPITHELIAL cells
*GENES
*IMMUNOGLOBULINS
*INFARCTION
*PHENOMENOLOGY
*MICE
*PATHOLOGIC neovascularization
*DISEASE complications
*METABOLISM
Subjects
Details
- Language :
- English
- ISSN :
- 17422094
- Volume :
- 13
- Database :
- Academic Search Index
- Journal :
- Journal of Neuroinflammation
- Publication Type :
- Academic Journal
- Accession number :
- 117883497
- Full Text :
- https://doi.org/10.1186/s12974-016-0697-1