Diabetic impairments in NO-mediated endothelial progenitor cell mobilization and homing are reversed by hyperoxia and SDF-1α

Gallagher, Katherine A.; Liu, Zhao Jun; Xiao, Min; Chen, Haiying; Goldstein, Lee J.; Buerk, Donald G.; Nedeau, April E.; Thom, Stephen R.; Velázquez, Omaida C.

doi:10.1172/jci29710

Cited by 605 publications

(562 citation statements)

References 56 publications

(71 reference statements)

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“…11 Vasculogenesis and the Role of eNOS and NO Our current understanding of vasculogenesis has developed rapidly over the past few years, and the characterization of EPCs, which migrate from the bone marrow in response to vasculogenic signaling molecules, is the subject of several excellent review articles. 17,[19][20][21][22][23][24] The role of VEGF in angiogenesis is well known, and its role in vasculogenesis has recently been elucidated (reviewed in Duda et al 25 ). Angiogenic growth factors, including VEGF, signal through their receptors to activate eNOS, which catalyzes the breakdown of L-arginine to L-citrulline and NO (Figure 4).…”

Section: Psma Expression In Tumor Neovasculaturementioning

confidence: 99%

“…Angiogenic growth factors, including VEGF, signal through their receptors to activate eNOS, which catalyzes the breakdown of L-arginine to L-citrulline and NO (Figure 4). The importance of both eNOS and NO in EPC mobilization and vasculogenesis has recently been characterized in the setting of diabetic wound healing 21,23 and in asthma vascular remodeling. 26 Inhibitors of eNOS decrease VEGF-induced angiogenesis.…”

Section: Psma Expression In Tumor Neovasculaturementioning

confidence: 99%

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Prostate-specific membrane antigen expression in regeneration and repair

et al. 2008

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Prostate-specific membrane antigen is a type II transmembrane glycoprotein, expressed in benign and neoplastic prostatic tissue as well as endothelial cells of neovasculature from a variety of tumors. The expression of prostate-specific membrane antigen in nonneoplastic neovasculature has not been well studied. Therefore, we studied nonneoplastic reparative and regenerative human tissues, as well as preneoplastic tissue, to determine the presence of prostate-specific membrane antigen-expressing neovasculature. Formalinfixed paraffin-embedded tissue from keloids, granulation tissue from heart valves and pleura, proliferative and secretory endometrium, and Barrett's mucosa with and without dysplasia were stained for the expression of prostate-specific membrane antigen (3E6). Vessels of proliferative, mid-secretory, and late secretory endometrium were consistently strongly positive for prostate-specific membrane antigen expression in all ten cases of each type (100%). Vessels associated with granulation tissue from pleural peels and heart valves were positive in 10 of 12 cases (83%) and 7 of 10 cases (70%), respectively. Keloids had prostate-specific membrane antigen-expressing endothelial cells in 6 of 15 cases (40%). Prostate-specific membrane antigen was not expressed by vessels associated with Barrett's mucosa with low-grade dysplasia (12 foci), high-grade dysplasia (24 foci), or no dysplasia (18 foci). A variety of nonneoplastic neovasculature expresses prostatespecific membrane antigen, including vessels in proliferative endometrium, granulation tissue, and some scars. This is the first study showing that prostate-specific membrane antigen is expressed in neovasculature from physiologic regenerative and reparative conditions. The folate hydrolase activity of prostate-specific membrane antigen may facilitate vasculogenesis and angiogenesis by increasing local availability of folic acid. These findings will enhance our overall understanding of blood vessel development and will enable us to better understand the effects of anti-prostate-specific membrane antigen therapies, which are already being explored in clinical trials.

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Section: Psma Expression In Tumor Neovasculaturementioning

confidence: 99%

Section: Psma Expression In Tumor Neovasculaturementioning

confidence: 99%

Prostate-specific membrane antigen expression in regeneration and repair

et al. 2008

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“…For example, SDF-1, VEGF, sphingosine-1-phosphate (S1P), and other soluble prosurvival factors, are upregulated in the hypoxic tissue and have been shown to play key roles in directing EPC migration. 2,25,43,85 VEGF, a key growth factor involved in both angiogenesis and vasculogenesis, has been shown to mobilize BM-derived progenitors into circulation. 5,45 A central chemokine involved in EPC homing, SDF-1, is also produced within the hypoxic stem cell niches of the BM and mediates chemotaxis of various cell types that express the receptor CXCR4.…”

Section: Matrix Modulation In Vascular Diseasesmentioning

confidence: 99%

“…17 SDF-1 production is also decreased in diabetic wounds, wherein exogenous administration of recombinant SDF-1 was shown to restore EPC recruitment in mice. 25,45 Additionally, while their HDL levels are high, patients with clinical evidence of vascular disease tend to have low levels of S1P in the HDL-containing fraction of serum. 84 This correlation between S1P and HDL has been suggested to contribute to the progression of atherosclerosis and may serve as a biomarker for individuals that are susceptible to ischemic heart disease but lack conventional risk factors such as low HDL-cholesterol.…”

Section: Matrix Modulation In Vascular Diseasesmentioning

confidence: 99%

The Role of Synthetic Extracellular Matrices in Endothelial Progenitor Cell Homing for Treatment of Vascular Disease

Williams

Silva

2015

Ann Biomed Eng

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“…In vitro studies have shown that eNOS/NO signaling enhance the mobilization, homing, and adhesion of EPCs (35,36). eNOS/NO signaling is associated with BPD (13).…”

Section: Lung Enos and Vegf Were Increased When Combining Epcs Transpmentioning

confidence: 99%

Combined iNO and endothelial progenitor cells improve lung alveolar and vascular structure in neonatal rats exposed to prolonged hyperoxia

Sun

Qian

2015

Pediatr Res

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Background: Stem cells or inhaled nitric oxide (iNO) are reported to improve lung structures in bronchopulmonary dysplasia (BPD) models. We hypothesized that combined iNO and transplanted endothelial progenitor cells (EPCs) might restore lung structure in rats after neonatal hyperoxia. Methods: Litters were separated into eight groups: room air, hyperoxia, hyperoxia + iNO, hyperoxia + iNO + L-NAME, hyperoxia + EPCs, hyperoxia + EPCs + L-NAME, hyperoxia + EPCs + iNO, and hyperoxia + EPCs + iNO + L-NAME. Litters were exposed to hyperoxia from the 21st day, then, sacrificed. EPCs were injected on the 21st day. L-NAME was injected daily for 7 d from the 21st day. Serum vascular endothelial growth factor (VEGF), radial alveolar count (RAC), VIII factor, EPCs engraftment, lung VEGF, VEGFR2, endothelial nitric oxide (eNOS) and SDF-1 expression, and NO production were examined. results: Hyperoxia exposure led to air space enlargement, loss of lung capillaries, and low expression of VEGF and eNOS. Transplanted EPCs, when combined with iNO, had significantly increased engraftment in lungs, compared to EPCs alone, upon hyperoxia exposure. There was improvement in alveolarization, microvessel density, and upregulation of VEGF and eNOS proteins in the hyperoxia-exposed EPCs with iNO group, compared to hyperoxia alone. conclusion: Combined EPCs and iNO improved lung structures after neonatal hyperoxia. This was associated with the upregulation of VEGF and eNOS expression.B ronchopulmonary dysplasia (BPD) is a chronic lung disease associated with significant mortality and morbidity in premature infants. New BPD is characterized by arrested alveolar and vascular growth (vascular hypothesis of BPD) (1,2). Alveolar formation is a highly coordinated process between the development of airways and pulmonary vasculature (3). Exposure to inflammation caused by excessive O 2 supplementation is hypothesized to interfere with the coordinated process of normal human lung development. Neonatal hyperoxia exposure is known to disrupt alveolar formation and growth, providing a useful model for studying BPD (4).Cell-based therapy is a novel approach that offers much promise in the prevention and treatment of BPD, including embryonic stem cells, mesenchymal stem cells, placental stem cells, umbilical cord stem cells, amniotic fluid and amnionderived cells, and lung progenitor cells. Endothelial progenitor cells (EPCs) are precursors of endothelial cells, which have the capacity of self-renewal and proliferation. EPCs is one of the key cells mediating vascular growth, which can mobilize from bone marrow and home to the site of vascular injuries, promoting neovascularization (5). There is data showing that reduced numbers or dysfunction of EPCs at birth is associated with the development of BPD (6,7). In addition, a reduction in the number of EPCs in the bone marrow, circulation and lungs has also emerged in animal models of BPD (8). Evidences that angiogenic cells treatment can restore lung structure have been demonstrated. Balasubramaniam et al...

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Diabetic impairments in NO-mediated endothelial progenitor cell mobilization and homing are reversed by hyperoxia and SDF-1α

Cited by 605 publications

References 56 publications

Prostate-specific membrane antigen expression in regeneration and repair

Prostate-specific membrane antigen expression in regeneration and repair

The Role of Synthetic Extracellular Matrices in Endothelial Progenitor Cell Homing for Treatment of Vascular Disease

Combined iNO and endothelial progenitor cells improve lung alveolar and vascular structure in neonatal rats exposed to prolonged hyperoxia

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