SDF-1α involved in mobilization and recruitment of endothelial progenitor cells after arterial injury in mice

Yin, Yi; Zhao, Xinshu; Fang, Yuqiang; Yu, Shiyong; Zhao, Jinghong; Song, Mingbao; Huang, Lan

doi:10.1016/j.carpath.2009.04.002

“…18 Gating of Sca1 + Flk1 + cells, which we found to be also Cd31 + , has recurrently been used in mice to quantify such circulating EPCs. [15][16][17] Furthermore, induced pluripotent stem cell-derived Flk1 + cells were recently shown to prevent injury-induced neointimal thickening in mice through enhanced reendothelialization, 39 supporting a role for Flk1 + progenitor cells in injury-induced endothelial repair. However, whether EPCs contribute to endothelial repair through differentiation into ECs and integration in the injured endothelium, or rather through paracrine effects on resident ECs through secretion of stimulatory molecules, is still heavily debated.…”

Section: Apoementioning

confidence: 99%

“…21 For example, systemic injection or local treatment of injured arteries with purified EPCs significantly enhanced reendothelialization and reduced neointimal thickening in mouse or rabbit injury models. 17,[32][33][34] These beneficial effects were further enlarged when the EPCs were pretreated with the protein kinase GSK3-β (glycogen synthase kinase 3 beta), which improved the adhesion capacity of the injected EPCs. 34 Furthermore, cilostazol treatment of rats significantly reduced neointimal hyperplasia after balloon carotid denudation, which was associated with an enhanced reendothelialization in vivo and an increased mobilization, proliferation, and differentiation capacity of EPCs in vitro.…”

Section: Cd31mentioning

confidence: 99%

“…41 In the context of carotid artery injury in mice, antibody-mediated blocking of Cxcr4 on EPCs significantly reduced their adhesion rate to injured arteries ex vivo and in vivo 17,23 and abolished the capacity of infused EPCs to promote endothelial recovery and reduce neointimal hyperplasia after vascular injury. 17,42 In contrast, overexpression of Cxcr4 enhanced the adhesion and Cxcl12-induced migration ability of EPCs in vitro and significantly increased the capacity of EPCs to promote injury-induced reendothelialization. a reduced immobilization of Cxcl12 on Cxcr4-deficient endothelium or could be related to a decreased endothelial Cxcl12 expression, given that Cxcl12 and endothelial apoptotic bodies generated after endothelial injury trigger endothelial Cxcl12 expression through a Cxcr4-mediated positive feedback loop.…”

mentioning

confidence: 99%

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Deficiency of Endothelial Cxcr4 Reduces Reendothelialization and Enhances Neointimal Hyperplasia After Vascular Injury in Atherosclerosis-Prone Mice

Noels

¹

,

Zhou

²

,

Tilstam

³

et al. 2014

ATVB

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Objective— The Cxcl12/Cxcr4 chemokine ligand/receptor axis mediates the mobilization of smooth muscle cell progenitors, driving injury-induced neointimal hyperplasia. This study aimed to investigate the role of endothelial Cxcr4 in neointima formation. Approach and Results— β-Galactosidase staining using bone marrow x kinase ( Bmx ) -CreER T2 reporter mice and double immunofluorescence revealed an efficient and endothelial-specific deletion of Cxcr4 in Bmx-CreER T2+ compared with Bmx-CreER T2− Cxcr4-floxed apolipoprotein E–deficient ( Apoe −/− ) mice (referred to as Cxcr4 EC-KO ApoE −/− and Cxcr4 EC-WT ApoE −/− , respectively). Endothelial Cxcr4 deficiency significantly increased wire injury–induced neointima formation in carotid arteries from Cxcr4 EC-KO ApoE −/− mice. The lesions displayed a higher number of macrophages, whereas the smooth muscle cell and collagen content were reduced. This was associated with a significant reduction in reendothelialization and endothelial cell proliferation in injured Cxcr4 EC-KO ApoE −/− carotids compared with Cxcr4 EC-WT ApoE −/− controls. Furthermore, stimulation of human aortic endothelial cells with chemokine (C-X-C motif) ligand 12 (CXCL12) significantly enhanced their wound-healing capacity in an in vitro scratch assay, an effect that could be reversed with the CXCR4 antagonist AMD3100. Also, flow cytometric analysis showed a reduced mobilization of Sca1 + Flk1 + Cd31 + and of Lin − Sca1 + progenitors in Cxcr4 EC-KO ApoE −/− mice after vascular injury, although Cxcr4 surface expression was unaltered. No differences could be detected in plasma concentrations of Cxcl12, vascular endothelial growth factor, sphingosine 1-phosphate, or Flt3 (fms-related tyrosine kinase 3) ligand, all cytokines with an established role in progenitor cell mobilization. Nonetheless, double immunofluorescence revealed a significant reduction in local endothelial Cxcl12 staining in injured carotids from Cxcr4 EC-KO ApoE −/− mice. Conclusions— Endothelial Cxcr4 is crucial for efficient reendothelialization after vascular injury through endothelial wound healing and proliferation, and through the mobilization of Sca1 + Flk1 + Cd31 + cells, often referred to as circulating endothelial progenitor cells.

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“…SDF-1α is abundantly produced in bone marrow and hypoxic area. 31,32 In bone marrow, SDF-1α plays an essential role retaining neutrophils and hematopoietic stem cells.…”

Section: Kobayashi Et Al Sdf-1α Enhances Endothelial Cell Barrier Intmentioning

confidence: 99%

“…SDF-1α is abundantly produced in bone marrow and hypoxic area. 31,32 In bone marrow, SDF-1α plays an essential role retaining neutrophils and hematopoietic stem cells.1,33 SDF-1α-induced bone marrow endothelial barrier enhancement may be involved, at least partially, in this myeloid cell retention. SDF-1α is also involved in cardiovascular disease.…”

mentioning

confidence: 99%

Stromal Cell–Derived Factor-1α/C-X-C Chemokine Receptor Type 4 Axis Promotes Endothelial Cell Barrier Integrity via Phosphoinositide 3-Kinase and Rac1 Activation

Kobayashi

¹

,

Sato

²

,

Kida

³

et al. 2014

ATVB

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Objective-Although stromal cell-derived factor (SDF)-1α is well known to modulate the mobilization of hematopoietic stem cells and endothelial progenitor cells, its effects on some pre-existing vascular functions remain unknown. We have investigated here the role of SDF-1α signaling in endothelial barrier function. Approach and Results-Treatment with SDF-1α elevated transendothelial electrical resistance and inhibited the dextran hyperpermeability elicited by thrombin in bovine aortic endothelial cells, both indicating an increase in endothelial barrier function. SDF-1α binds to 2 receptors, C-X-C chemokine receptor types 4 and 7 (CXCR4 and CXCR7). Pretreatment with a CXCR4 antagonist or CXCR4 gene depletion by small interfering RNA (siRNA) eliminated SDF-1α-induced endothelial barrier enhancement. In contrast, CXCR7 antagonist or CXCR7 gene depletion by siRNA did not influence SDF-1α-induced barrier enhancement. Pretreatment with a Gi-protein inhibitor, a phosphoinositide 3-kinase (PI3K) inhibitor, or PI3K p110γ subunit gene depletion by siRNA also inhibited SDF-1α-induced barrier enhancement significantly. Western blot analysis revealed that SDF-1α phosphorylated Akt Ser473 in endothelial cells, suggesting PI3K activation. Immunostaining showed that treatment with SDF-1α formed a cortical actin rim, which was accompanied by Rac1 activation. In vivo, SDF-1α inhibited croton oil-induced vascular leakage indexed by dye extravasation, which is attenuated by a pretreatment with a CXCR4 antagonist. ). These cellular responses cause cytoskeletal rearrangement and adherens junction disassembly leading to barrier disruption. Conclusions-We9 Vascular endothelial growth factor stimulates receptor tyrosine kinase to produce NO, which disrupts cell-cell adhesion and increases barrier permeability. 10 In contrast, S1P is well known to enhance EC adhesion and barrier formation strongly via activation of its Gi protein-coupled receptor and its downstream signaling molecules, phosphoinositide 3-kinase (PI3K) and Rac1 GTPase.9,11 Because of their adhesion-promoting properties, these barrier regulatory molecules can be considered possible therapeutic targets against various types of inflammatory diseases. 8,12,13 The discovery of a novel vascular barrier modulator and the elucidation of its mechanism of action could also provide new opportunities for the treatment of inflammatory diseases.In the present study, we have attempted to elucidate whether and how SDF-1α modulates vascular endothelial permeability. We have found that the SDF-1α/CXCR4 axis promotes barrier enhancement in vascular ECs. Materials and MethodsMaterials and Methods are available in the online-only Supplement. Results SDF-1α Promotes Endothelial Barrier IntegrityAs shown in Figure 1A and 1B, SDF-1α (1-100 ng/mL) dose dependently increased transendothelial electrical resistance (TER) in bovine aortic ECs (BAECs), indicating endothelial barrier enhancement. TER reached a peak 10 minutes after SDF-1α stimulation and returned to a basal level within 75 minutes. T...

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Nanotechnology in Coronary Artery Stent Coating

Liu

¹

,

Chen

²

2016

Biomedical Nanomaterials

1

0

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SDF-1α involved in mobilization and recruitment of endothelial progenitor cells after arterial injury in mice

Cited by 63 publications

References 40 publications

Deficiency of Endothelial Cxcr4 Reduces Reendothelialization and Enhances Neointimal Hyperplasia After Vascular Injury in Atherosclerosis-Prone Mice

Deficiency of Endothelial Cxcr4 Reduces Reendothelialization and Enhances Neointimal Hyperplasia After Vascular Injury in Atherosclerosis-Prone Mice

Stromal Cell–Derived Factor-1α/C-X-C Chemokine Receptor Type 4 Axis Promotes Endothelial Cell Barrier Integrity via Phosphoinositide 3-Kinase and Rac1 Activation

Nanotechnology in Coronary Artery Stent Coating

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