Pharmacologic Targeting of Endothelial Progenitor Cells

Albiero, Mattia; Menegazzo, Lisa; Avogaro, Angelo; Fadini, Gian Paolo

doi:10.2174/187152910790780087

Cited by 11 publications

(8 citation statements)

References 191 publications

(250 reference statements)

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“…Thus, it appears that both lysates do not affect EPCs functional activities in a dose dependent manner, while the largest effects of LJ on viability and adhesion capacity occur at the lowest concentrations ( Figures 1 – 3 , panels A). A double-edged or biphasic action on EPCs with no or detrimental effects at higher-doses has been reported for several compounds including statins, thiazolidinediones and even insulin [44] , [56] . Also resveratrol, at low doses promotes antioxidant effects while at higher doses can have a dose-dependent pro-oxidant role followed by cell damage and apoptosis [57] .…”

Section: Discussionmentioning

confidence: 96%

“…Recently EPCs number and function have become the target of pharmaceutical compounds such as statins, renin-angiotensin system blockers, and some classes of glucose-lowering agents (thiazolidinediones and dipeptidyl peptidase-4 inhibitors) [44] , [45] ; furthermore, several natural anti-oxidative compounds with anti-inflammatory properties have also been found to enhance EPCs bioactivity, even if large clinical trials testing the effects of antioxidants on cardiovascular risk resulted in systematic failures [46] , [47] . These disappointing results are probably related to the limited effects of traditional antioxidants on intracellular ROS production, while they exert a scavenging action on already formed ROS [48] .…”

Section: Discussionmentioning

confidence: 99%

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Grain and Bean Lysates Improve Function of Endothelial Progenitor Cells from Human Peripheral Blood: Involvement of the Endogenous Antioxidant Defenses

et al. 2014

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Increased oxidative stress contributes to the functional impairment of endothelial progenitor cells (EPCs), the pivotal players in the servicing of the endothelial cell lining. Several evidences suggest that decreasing oxidative stress by natural compounds with antioxidant properties may improve EPCs bioactivity. Here, we investigated the effects of Lisosan G (LG), a Triticum Sativum grain powder, and Lady Joy (LJ), a bean lysate, on function of EPCs exposed to oxidative stress. Peripheral blood mononuclear cells were isolated and plated on fibronectin-coated culture dishes; adherent cells, identified as early EPCs, were pre-treated with different concentrations of LG and LJ and incubated with hydrogen peroxide (H2O2). Viability, senescence, adhesion, ROS production and antioxidant enzymes gene expression were evaluated. Lysate-mediated Nrf-2 (nuclear factor (erythroid-derived 2)-like 2)/ARE (antioxidant response element) activation, a modulator of oxidative stress, was assessed by immunocytochemistry. Lady Joy 0.35–0.7 mg/ml increases EPCs viability; pre-treatment with either LG 0.7 mg/ml and LJ 0.35–0.7 mg/ml protect EPCs viability against H2O2-induced injury. LG 0.7 and LJ 0.35–0.7 mg/ml improve EPCs adhesion; pre-treatment with either LG 0.35 and 0.7 mg/ml or LJ 0.35, 0.7 and 1.4 mg/ml preserve adhesiveness of EPCs exposed to H2O2. Senescence is attenuated in EPCs incubated with lysates 0.35 mg/ml. After exposure to H2O2, LG pre-treated cells show a lower senescence than untreated EPCs. Lysates significantly decrease H2O2-induced ROS generation. Both lysates increase glutathione peroxidase-1 and superoxide dismutase-2 (SOD-2) expression; upon H2O2 exposure, pre-treatment with LJ allows higher SOD-2 expression. Heme oxigenase-1 increases in EPCs pre-treated with LG even upon H2O2 exposure. Finally, incubation with LG 0.7 mg/ml results in Nrf-2 translocation into the nucleus both at baseline and after the oxidative challenge. Our data suggest a protective effect of lysates on EPCs exposed to oxidative stress through the involvement of antioxidant systems. Lisosan G seems to activate the Nrf-2/ARE pathways.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Grain and Bean Lysates Improve Function of Endothelial Progenitor Cells from Human Peripheral Blood: Involvement of the Endogenous Antioxidant Defenses

et al. 2014

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“…Circulating bone marrow derived cells, defined as early endothelial progenitor cells (EPCs), can proliferate multiple times and differentiate into endothelial cells [30–31]. Recent studies have shown that mobilization and differentiation of EPCs play an important role in augmenting neovascularization and endothelial replacement in the ischemic and injured heart [32–34].…”

Section: Discussionmentioning

confidence: 99%

A potent soluble epoxide hydrolase inhibitor, t-AUCB, acts through PPARγ to modulate the function of endothelial progenitor cells from patients with acute myocardial infarction

Xu¹,

Davis²,

Wang³

et al. 2013

International Journal of Cardiology

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Background Epoxyeicosatrienoic acids (EETs) are natural angiogenic mediators regulated by soluble epoxide hydrolase (sEH). Inhibitors of sEH can stabilize EETs levels and were reported to reduce atherosclerosis and inhibit myocardial infarction in animal models. In this work, we investigated wether increasing EETs with the sEH inhibitor t-AUCB would increase angiogenesis related function in endothelial progenitor cells (EPCs) from patients with acute myocardial infarction (AMI). Methods and Results EPCs were isolated from 50 AMI patients and 50 healthy subjects (control). EPCs were treated with different concentrations of t-AUCB for 24 hours with or without peroxisome proliferator activated receptor γ (PPARγ) inhibitor GW9662. Migration of EPCs was assayed in trans-well chambers. Angiogenesis assays were performed using a Matrigel-Matrix in vitro model. The expression of vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1α (HIF-1α) mRNA and protein in EPCs were measured by real-time PCR or Western blot, respectively. Also, the concentration of EETs in the culture supernatant was detected by ELISA. The activity of EPCs in the AMI patient group was reduced compared to healthy controls. Whereas increasing EET levels with t-AUCB promoted a dose dependent angiogenesis and migration in EPCs from AMI patients. Additionally, the t-AUCB dose dependently increased the expression of the angiogenic factors VEGF and HIF-α. Lastly, we showed that these effects were PPARγ dependent. Conclusion The results demonstrate that the sEH inhibitor positively modulated the functions of EPCs in patients with AMI through the EETs-PPARγ pathway. The present study suggests the potential utility of sEHi in the therapy of ischemic heart disease.

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“…Once in the bloodstream, EPC specifically home to sites of vascular damage through chemokine sensing, e.g. via the CXCR4/SDF-1a or the RANTES / CCR5 axis, the IL-8 / GRO-CXC system interacting with CXCR2, as well as 2-integrins and Eselectin [56]. After adhesion to the local endothelial layer, EPCs either act as a cell patch to repair endothelial discontinuity or migrate through the interstitium and participate in the formation of new blood vessels.…”

Section: Estrogens Serms and Endothelial Progenitor Cellsmentioning

confidence: 99%

“…As a result, even in the presence of a normal ischemic mobilization, EPCs would be unable to repair a damaged tissue. For all these reasons, ways to stimulate EPC-mediated cardiovascular repair are actively pursued [56]. Iwakura et al first documented that estrogens are essential for the ability of EPCs to repair an experimental arterial injury.…”

Section: Estrogens Serms and Endothelial Progenitor Cellsmentioning

confidence: 99%

Enhancing Endothelial Progenitor Cell Function Through Selective Estrogen Receptor Modulation: A Potential Approach to Cardiovascular Risk Reduction

Cignarella

Fadini

2010

CHAMC

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Estrogen receptors (ER) have been targets of pharmacological intervention for decades. The use of menopausal hormone therapy (MHT) for improving cardiovascular health is associated with serious adverse effects and therefore cannot be recommended as a first-line strategy. While recently menopausal women in good cardiovascular health may be more likely to benefit from MHT than older women with worse risk profiles, adverse MHT effects such as increased risk for stroke have been consistently shown. Selective estrogen receptor modulators (SERMs) such as tamoxifen and raloxifene have been developed to avoid such negative aspects of MHT. Based on available evidence, however, SERMs are not endowed with greater cardiovascular efficacy and safety than conventional MHT. By contrast, the newly developed SERM lasofoxifene has been shown to reduce cardiovascular events in post-menopausal women, although it also increased venous thromboembolic events in line with other ER-targeting agents. Fundamental research has shown that endothelial progenitor cells are important targets of estrogen actions in the cardiovascular system. This indicates that preferential targeting of specific cells and tissues is likely to enhance safety over nonselective hormone agents. Similarly, increased ER-isoform selectivity along with deeper understanding of ER biology should assist in designing novel ER modulators that are more effective and safer than currently used agents. In this article, we summarize the potential connections between SERMs and EPC biology, uncovering novel possible routes to cardiovascular risk reduction.

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Pharmacologic Targeting of Endothelial Progenitor Cells

Cited by 11 publications

References 191 publications

Grain and Bean Lysates Improve Function of Endothelial Progenitor Cells from Human Peripheral Blood: Involvement of the Endogenous Antioxidant Defenses

Grain and Bean Lysates Improve Function of Endothelial Progenitor Cells from Human Peripheral Blood: Involvement of the Endogenous Antioxidant Defenses

A potent soluble epoxide hydrolase inhibitor, t-AUCB, acts through PPARγ to modulate the function of endothelial progenitor cells from patients with acute myocardial infarction

Enhancing Endothelial Progenitor Cell Function Through Selective Estrogen Receptor Modulation: A Potential Approach to Cardiovascular Risk Reduction

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