Current perspective of pathophysiological and interventional effects on endothelial progenitor cell biology: Focus on Pi3K/AKT/eNOS pathway

Everaert, Bert; Craenenbroeck, Emeline M. Van; Hoymans, Vicky Y.; Haine, Steven; Nassauw, Luc Van; Conraads, Viviane M.; Timmermans, Jean‐Pierre; Vrints, Christiaan J.

doi:10.1016/j.ijcard.2010.04.018

Cited by 91 publications

(60 citation statements)

References 204 publications

(221 reference statements)

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“…Of the two previous studies, one included only subjects taking no medications (13); while the other study included participants taking medications (11), the proportion of subjects on statins and anti-hypertensive medications was lower than that in the present report. Within this study, a greater percentage of individuals in the T2DM group, compared with the IGT or NGT groups, were on medications such as statins and angiotensin-converting enzyme inhibitors, which are associated with higher circulating CD34ϩ hematopoetic progenitor cell number (9). As there was a tendency for those taking statins to have higher basal CD34ϩ hematopoetic progenitor cell number, this could explain the relatively higher CD34ϩ cell number in the T2DM subjects in this study.…”

Section: Discussionmentioning

confidence: 73%

“…We also did not control for medication use across our groups of participants, so we could not formally analyze the effect of specific medications on the number or mobilization of cells. There are several medications, including statins, that appear to increase circulating EPC number (9). If these did affect CD34ϩ/ VEGFR2ϩ EPC number in our subjects, we may actually have underestimated the lower EPC number and mobilization in the IGT and T2DM groups.…”

Section: Discussionmentioning

confidence: 89%

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Exercise-induced endothelial progenitor cell mobilization is attenuated in impaired glucose tolerance and type 2 diabetes

et al. 2016

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Lutz AH, Blumenthal JB, Landers-Ramos RQ, Prior SJ. Exercise-induced endothelial progenitor cell mobilization is attenuated in impaired glucose tolerance and type 2 diabetes. J Appl Physiol 121: 36 -41, 2016. First published May 19, 2016 doi:10.1152/japplphysiol.00349.2016.-Circulating endothelial progenitor cells (EPCs) contribute to vascular homeostasis and are fewer in those with type 2 diabetes mellitus (T2DM) compared with normal glucose tolerance (NGT), suggesting a link between EPCs and T2DM-associated vasculopathies. The purpose of this study was to assess EPC number and mobilization by acute submaximal exercise in older adults with NGT, impaired glucose tolerance (IGT) or T2DM. We tested the hypothesis that EPC mobilization is lower in IGT compared with NGT and further reduced in older adults with T2DM. Forty-five older (50-75 yr of age) men and women with NGT (n ϭ 18), IGT (n ϭ 10), or T2DM (n ϭ 17) were characterized and underwent submaximal aerobic exercise tests with blood sampling for enumeration of vascular endothelial growth factor receptor 2ϩ (VEGFR2ϩ) cells, CD34ϩ hematopoetic progenitor cells, and CD34ϩ/VEGFR2ϩ EPCs by flow cytometry before and after exercise. Basal EPC number was 65 and 61% lower in the IGT and T2DM groups, respectively, compared with the NGT group (P Ͻ 0.05). EPC number increased 23% after acute exercise in the NGT group (P Ͻ 0.01), but did not change in the IGT or T2DM groups. Before and after exercise, VEGFR2ϩ cell number was lower in a stepwise manner across the NGT, IGT, and T2DM groups (P Ͻ 0.05). Basal CD34ϩ cell number was lower in the IGT group compared with NGT (P Ͻ 0.05), but did not change after exercise in any group. These findings suggest a CD34ϩ/VEGFR2ϩ EPC mobilization defect in IGT and T2DM that could play a role in the cardiovascular diseases and capillary rarefaction associated with insulin resistance.

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Section: Discussionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 89%

Exercise-induced endothelial progenitor cell mobilization is attenuated in impaired glucose tolerance and type 2 diabetes

et al. 2016

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“…Established evidence indicates that the Akt/eNOS pathway plays a pivotal role in the regulation of EPCs (10). In turn, eNOS modulates EPC mobilization, migration, and survival via the generation of NO (10). In an ex vivo study (17), the migration and tube formation ability of early and late EPCs were related to NO.…”

Section: Discussionmentioning

confidence: 97%

Akt/eNOS signaling pathway mediates inhibition of endothelial progenitor cells by palmitate-induced ceramide

Tan

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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Palmitate (PA) impairs endothelial progenitor cells (EPCs). However, the molecular mechanism underlying the suppressive function of PA remains largely unknown. Ceramide, a free fatty acid metabolite, mediates multiple cellular signals. We hypothesized that ceramide acts as an intermediate molecule to mediate inhibition of EPCs by PA. We first demonstrated that PA could inhibit the attachment, migration, and tube formation of EPCs through suppression of the Akt/endothelial nitric oxide (NO) synthase (eNOS) signaling pathway. In addition, we observed that PA could induce ceramide accumulation in EPCs. To test whether the accumulation of ceramide causes EPC dysfunction, the ceramide synthesis inhibitors myriocin and fumonisin B1 were used. We that found both inhibitors could effectively abolish PA-mediated EPC inhibition. Furthermore, the ceramide deacylation inhibitor N-oleoylethanolamine could augment the inhibitory effect of PA on EPCs, indicating that it is ceramide, not its metabolites, that mediates the suppression of EPCs by PA. We have previously shown that Akt/ eNOS phosphorylation was reduced after PA treatment, which, in turn, hampered the normal bioavailability of NO, leading to impaired functions of EPCs. To test the role for ceramide in this process, a clinically used NO donor, sodium nitroprusside, was used. We found that sodium nitroprusside could rescue the suppressive effects of ceramide on EPCs, suggesting that ceramide-mediated EPC inhibition might be through reduction of NO production. Taken together, our findings indicated that ceramide-induced reduction of NO might be the molecular mechanism for PA-mediated EPC inhibition; thus, targeting either ceramide or NO production might be an effective means for improvement of EPC functions in diseases.

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“…Other studies have reported that UII and GPR14 are expressed at high levels in atherosclerotic plaques and injured myocardium (3,11). For more than a decade, EPCs have been implicated in cardiovascular homeostasis (12)(13)(14). Expression of GPR14 in EPCs further indicated that UII exerts its function through the increase of UII concentration in circulation and local tissue (4).…”

Section: Discussionmentioning

confidence: 99%

Urotensin II promotes the proliferation of endothelial progenitor cells through p38 and p44/42 MAPK activation

Wen

Jiang

2012

Mol Med Report

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Abstract. Urotensin II (UII) is a vasoactive peptide with many potent effects in the cardiorenovascular system and is also possibly involved in the pathogenesis of atherosclerosis. Endothelial progenitor cells (EPCs) are involved in angiogenesis and vascular homeostasis and may be important in the maintenance of endothelial integrity. The aim of this study was to investigate whether UII has an effect on the proliferation of bone marrow-derived EPCs and the possible signaling mechanisms involved. Bone marrow-derived EPCs were isolated from male Sprague-Dawley rats and cultured in medium containing 5% fetal bovine serum. Cells were incubated with UII for 24 h. The proliferation of EPCs was analyzed by MTT assay. Western blotting was performed to determine the phosphorylation levels of mitogen-activated protein kinases (MAPKs). The results demonstrated that UII promoted the proliferation of EPCs in a concentrationdependent manner in a certain range, and the proliferation was largely suppressed by inhibitors of GPR14 and MAPKs (p38 and p44/42). UII significantly increased the phosphorylation levels of p38MAPK and p44/42MAPK, and these effects were significantly inhibited by respective inhibitors. These findings indicate that UII promotes the proliferation of rat bone marrow-derived EPCs through a process that involves MAPK activation, and provides novel insights regarding the role of UII in the EPC-mediated repair of atherosclerotic injury.

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Current perspective of pathophysiological and interventional effects on endothelial progenitor cell biology: Focus on Pi3K/AKT/eNOS pathway

Cited by 91 publications

References 204 publications

Exercise-induced endothelial progenitor cell mobilization is attenuated in impaired glucose tolerance and type 2 diabetes

Exercise-induced endothelial progenitor cell mobilization is attenuated in impaired glucose tolerance and type 2 diabetes

Akt/eNOS signaling pathway mediates inhibition of endothelial progenitor cells by palmitate-induced ceramide

Urotensin II promotes the proliferation of endothelial progenitor cells through p38 and p44/42 MAPK activation

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