CXCR4, a Key Modulator of Vascular Progenitor Cells

Sainz, Julie; Sata, Masataka

doi:10.1161/01.atv.0000256727.34148.e2

Cited by 50 publications

(43 citation statements)

References 27 publications

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“…The CXCR4 has been shown to be involved in the homing of EPCs (Hristov et al, 2007a;Sainz & Sata, 2007;Chen et al, 2010). Our data showed the surface CXCR4 protein expression did not have difference between young and elderly men (p = NS) (Fig.…”

Section: Introductionmentioning

confidence: 59%

“…There is increasing evidence that CXCR4 is a key regulator of homing and retention of EPCs at the sites of injured artery, suggesting that an enhanced CXCR4 expression may facilitate the endothelial repair capacity of EPCs (Hristov et al, 2007a;Sainz & Sata, 2007;Chen et al, 2010). However, the influences of physical exercise on endothelialization capacity and CXCR4 signaling of human EPCs are not clear in persons with aging.…”

Section: Introductionmentioning

confidence: 99%

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Physical exercise attenuates age‐associated reduction in endothelium‐reparative capacity of endothelial progenitor cells by increasing CXCR4/JAK‐2 signaling in healthy men

Xia¹,

Li²,

Su³

et al. 2011

Aging Cell

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SummaryEndothelial progenitor cells (EPCs) play an important role in repairing endothelial injury. Aging is associated with EPC dysfunction. Physical exercise has a beneficial impact on EPC activity. However, whether physical exercise can enhance the endothelial repair capacity of EPCs in healthy men with aging is not clear. Here, we investigated the effects of physical exercise on reendothelialization capacity and CXC chemokine receptor four (CXCR4) signaling in human EPCs. Before and after 12-week exercise, EPCs were isolated from elderly and young men. In vitro function and in vivo reendothelialization capacity of EPCs in a mouse model of carotid artery injury were measured. The expression of CXCR4 and its downstream signaling target Janus kinase-2 (JAK-2) were determined. Before exercise, in vitro function and in vivo reendothelialization capacity of EPCs were significantly reduced in elderly men compared with young men. After exercise intervention, in vitro function and in vivo reendothelialization capacity of EPCs from elderly men were markedly enhanced. Physical exercise increased a higher CXCR4 protein expression and higher JAK-2 phosphorylation levels of EPCs. The augmentation in reendothelialization capacity of EPCs was closely correlated with the upregulation of CXCR4 ⁄ JAK-2 signaling and improvement of endothelial function. This study demonstrates for the first time that physical exercise attenuates age-associated reduction in endotheliumreparative capacity of EPCs by increasing CXCR4 ⁄ JAK-2 signaling. Our findings provide insight into the novel mechanisms of physical exercise as a lifestyle intervention strategy to promote vascular health in aging population.

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Section: Introductionmentioning

confidence: 59%

Section: Introductionmentioning

confidence: 99%

Physical exercise attenuates age‐associated reduction in endothelium‐reparative capacity of endothelial progenitor cells by increasing CXCR4/JAK‐2 signaling in healthy men

Xia¹,

Li²,

Su³

et al. 2011

Aging Cell

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“…[26][27][28]30,31 Given the close association between CXCR4 signaling and EPCs targeted repair for endothelium, we hypothesized that disturbance in CXCR4 signaling is related to the impaired EPC function in the elderly. We show that SDF-1-induced phosphorylations of CXCR4 and JAK-2 are significantly lower in EPCs from the elderly than in EPCs from the young.…”

Section: Discussionmentioning

confidence: 99%

Age-Related Decline in Reendothelialization Capacity of Human Endothelial Progenitor Cells Is Restored by Shear Stress

Xia¹,

Yang²,

Xu³

et al. 2012

Hypertension

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Abstract-Aging is associated with dysfunction of endothelial progenitor cells (EPCs), and shear stress has a beneficial impact on EPC function; however, the effects of aging and shear stress on the endothelial repair capacity of EPCs after arterial injury have not been reported. Here we investigated the influence of aging and shear stress on the reendothelialization capacity of human EPCs and the related molecular mechanism. Compared with EPCs isolated from young subjects, EPCs from the elderly displayed an impaired migration and adhesion in vitro and demonstrated a significantly reduced reendothelialization capacity in vivo after transplantation into nude mice with carotid artery denudation injury. Shear stress pretreatment enhances the migration, adhesion, and reendothelialization capacity in both young and elderly EPCs; however, it was to a greater extent in EPCs from the elderly. Although basal CXC chemokine receptor 4 (CXCR4) expression was similar in EPCs from the 2 age groups, the stromal cell derived factor 1-induced CXCR4 and Janus kinase 2 phosphorylations were much lower in the elderly than in young EPCs. Shear stress treatment upregulated CXCR4 expression and phosphorylation and, importantly, restored the stromal cell-derived factor 1/CXCR4-dependent Janus kinase 2 phosphorylation in the elderly EPCs. Furthermore, short hairpin RNA-mediated knockdown of CXCR4 expression or pretreatment with Janus kinase 2 inhibitor diminished the enhancement in the migration, adhesion, and reendothelialization capacity of the elderly EPCs from shear stress treatments. Thus, our study demonstrates that upregulation of the CXCR4/Janus kinase 2 pathway by shear stress contributes to the enhanced reendothelialization capacity of EPCs from elderly men. A ging is a well-recognized risk factor for cardiovascular disease. 1,2 The impact of aging, a traditional detrimental factor, for the increased development of cardiovascular disease is initiated by abnormalities in structure and function of the vascular endothelium.3-5 Thus, it is of particular importance to maintain the integrity of the vascular endothelium after arterial injury with aging.Accelerated reendothelialization is an important therapeutic means for repair of injured artery. Accumulating evidence indicates that circulating endothelial progenitor cells (EPCs) provide an endogenous repair mechanism to counteract ongoing risk factor-induced endothelial injury and to replace dysfunctional endothelium, 6-10 thus suggesting an important role of circulating EPCs for restoration of the integrity of the vascular endothelium with aging. Previous studies showed that aging leads to a reduction in the number of circulating EPCs, and aging is associated with dysfunctional EPCs in both healthy persons and patients with cardiovascular disease, [11][12][13][14][15][16] which is, at least in part, responsible for the development of age-related endothelial injury in humans. [17][18][19] However, the mechanism underlying age-related EPC dysfunction is not fully understood. It is, t...

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“…26,27 The observed dynamics of adhesion, indeed, was associated with the enhancement of SDF-1 expression in the ischemic kidneys, as demonstrated by Togel et al 27 Therefore, we inquired whether CXCR4-SDF-1 interaction played a role in the observed changes of MSC adhesion to the kidney. Indeed, in the ischemic kidney sections MSC-4E cells tended to colocalize with the expression of SDF-1, which was only faintly detectable in control sections ( Figure 5).…”

Section: Dependence Of Adhesion On the Cxcr4-sdf-1 Interactionmentioning

confidence: 66%

Mesenchymal Stem Cells, Used As Bait, Disclose Tissue Binding Sites

Ratliff

Singh

Yasuda

et al. 2010

The American Journal of Pathology

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We developed an ex vivo approach characterizing renal mesenchymal stem cell (MSC) adhesion to kidney sections. Specificity of MSC adhesion was confirmed by demonstrating a) 3T3 cells displayed 10-fold lower adhesion, and b) MSC adhesion was CXCR4/stromal-derived factor-1 (SDF-1)-dependent. MSC adhesion was asymmetrical, with postischemic sections exhibiting more than twofold higher adhesion than controls, and showed preference to perivascular areas. Pretreating kidney sections with cyclic arginine-glycine-aspartic acid peptide resulted in increased MSC adhesion (by displacing resident cells), whereas blockade of CXCR4 with AMD3100 and inhibition of ␣4␤1 (VLA4)

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CXCR4, a Key Modulator of Vascular Progenitor Cells

Cited by 50 publications

References 27 publications

Physical exercise attenuates age‐associated reduction in endothelium‐reparative capacity of endothelial progenitor cells by increasing CXCR4/JAK‐2 signaling in healthy men

Physical exercise attenuates age‐associated reduction in endothelium‐reparative capacity of endothelial progenitor cells by increasing CXCR4/JAK‐2 signaling in healthy men

Age-Related Decline in Reendothelialization Capacity of Human Endothelial Progenitor Cells Is Restored by Shear Stress

Mesenchymal Stem Cells, Used As Bait, Disclose Tissue Binding Sites

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