Endothelial progenitor cells: diagnostic and therapeutic considerations

Liew, Aaron; Barry, Frank; O’Brien, Timothy

doi:10.1002/bies.20372

Cited by 85 publications

(65 citation statements)

References 99 publications

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“…36 The current study demonstrates for the first time that EPCs circulate in decreased numbers in the PB of patients with depression and, furthermore, opens a number of new perspectives in the pathogenesis of cardiovascular disorders in depression. However, although our results could be related to the EPC suppressive role of proinflammatory cytokines, further studies are needed to investigate the exact pathomolecular background of the connection between mood disorders and altered EPC counts.…”

Section: Discussionmentioning

confidence: 61%

“…36 However, these surface molecules are differentially expressed in late/mature and in early/ immature phenotypes and none of them by itself is specific for EPCs. The lack of a special and exclusive marker truly specific for EPCs dictates that combinations of the above markers must be used to best identify this cell population.…”

Section: Resultsmentioning

confidence: 99%

“…Recent studies suggest that a subset of these cells, EPCs, may contribute to ongoing vascular repair by providing a circulating cell population that can home to the blood vessel walls and incorporate into the injured endothelial tube to replace dysfunctional endothelial cells. 14,36 Consequently, impairment of this EPC pool is considered to have negative effects on the cardiovascular system and patients with reduced numbers of EPCs are at increased risk for endothelial injury and for arteriosclerotic plaque development. 20 A further established risk factor recognized today in the pathogenesis of arteriosclerosis and cardiovascular disorders is depression.…”

Section: Discussionmentioning

confidence: 99%

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Circulating endothelial progenitor cells and depression: a possible novel link between heart and soul

Döme

Teleki²,

Rihmer

et al. 2008

Mol Psychiatry

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Although depression is known to be an independent risk factor for cardiovascular disorders, the mechanisms behind this connection are not well understood. However, the reduction in the number of endothelial progenitor cells (EPCs) in patients with cardiovascular risk factors has led us to hypothesize that depression influences the number of EPCs. EPCs labeled with CD34, CD133 and vascular endothelial growth factor receptor-2 (VEGFR2) antibodies were counted by flow cytometry in the peripheral blood (PB) of 33 patients with a current episode of major depression and of 16 control subjects. Mature (CD34 þ /VEGFR2 þ ) and immature (CD133 þ / VEGFR2 þ ) EPC counts were decreased in patients (vs controls; P < 0.01 for both comparisons), and there was a significant inverse relationship between EPC levels and the severity of depressive symptoms (P < 0.01 for both EPC phenotypes). Additionally, we assayed the plasma levels of VEGF, C-reactive protein (CRP) and tumor necrosis factor (TNF)-a and observed significantly elevated TNF-a concentrations in patients (vs controls; P < 0.05) and, moreover, a significant inverse correlation between TNF-a and EPC levels (P < 0.05). Moreover, by means of a quantitative RT-PCR approach, we measured CD34, CD133 and VEGFR2 mRNA levels of PB samples and found a net trend toward a decrease in all the investigated EPC-specific mRNA levels in patients as compared with controls. However, statistical significance was reached only for VEGFR2 and CD133 levels (P < 0.01 for both markers). This is the first paper that demonstrates evidence of decreased numbers of circulating EPCs in patients with a current episode of major depression.

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Section: Discussionmentioning

confidence: 61%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Circulating endothelial progenitor cells and depression: a possible novel link between heart and soul

Döme

Teleki²,

Rihmer

et al. 2008

Mol Psychiatry

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“…Endothelial progenitor cells (EPCs) differentiate into endothelial cells whose function in vascular repair depends on chemokine-and growth factordirected cell migration. The role of EPCs in endothelial repair is supported by their ability to inhibit development of atherosclerosis (10,11) and intimal hyperplasia (12), while still promoting beneficial angiogenesis. We previously demonstrated the central role of the actin cytoskeleton in EPC migration (13), and our findings suggest that NO has a critical function within EPCs, where it regulates the distribution of vasodilator-stimulated phosphoprotein (VASP).…”

mentioning

confidence: 99%

Carbon Monoxide and Nitric Oxide Mediate Cytoskeletal Reorganization in Microvascular Cells via Vasodilator-Stimulated Phosphoprotein Phosphorylation

et al. 2008

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OBJECTIVE-We examined the effect of the vasoactive agents carbon monoxide (CO) and nitric oxide (NO) on the phosphorylation and intracellular redistribution of vasodilator-stimulated phosphoprotein (VASP), a critical actin motor protein required for cell migration that also controls vasodilation and platelet aggregation. RESEARCH DESIGN AND METHODS-We examined the effect of donor-released CO and NO in endothelial progenitor cells (EPCs) and platelets from nondiabetic and diabetic subjects and in human microvascular endothelial cells (HMECs) cultured under low (5.5 mmol/l) or high (25 mmol/l) glucose conditions. VASP phosphorylation was evaluated using phosphorylation site-specific antibodies.RESULTS-In control platelets, CO selectively promotes phosphorylation at VASP Ser-157, whereas NO promotes phosphorylation primarily at Ser-157 and also at Ser-239, with maximal responses at 1 min with both agents on Ser-157 and at 15 min on Ser-239 with NO treatment. In diabetic platelets, neither agent resulted in VASP phosphorylation. In nondiabetic EPCs, NO and CO increased phosphorylation at Ser-239 and Ser-157, respectively, but this response was markedly reduced in diabetic EPCs. In endothelial cells cultured under low glucose conditions, both CO and NO induced phosphorylation at Ser-157 and Ser-239; however, this response was completely lost when cells were cultured under high glucose conditions. In control EPCs and in HMECs exposed to low glucose, VASP was redistributed to filopodia-like structures following CO or NO exposure; however, redistribution was dramatically attenuated under high glucose conditions. CONCLUSIONS-Vasoactive gases CO and NO promote cytoskeletal changes through site-and cell type-specific VASP phosphorylation, and in diabetes, blunted responses to these agents may lead to reduced vascular repair and tissue perfusion. T he gaseous signal molecules nitric oxide (NO) and carbon monoxide (CO) exert multiple modulatory actions in regulating vascular function. While NO effects have been recognized for over a decade, similar vasoregulatory action of CO was established only recently. CO is generated by heme oxygenase (HO)-1 under a wide variety of conditions (e.g., cell exposure to such stressors as hypoxia, growth factors, and cytokine stimulation) that activate the enzyme (1,2). Unlike its highly reactive cognate NO, which participates in multiple redox reactions, CO is a relatively stable gas that exhibits extraordinary affinity for heme centers (3-5). Like NO, the signaling effects of CO rely in part on its ability to form a complex with the heme moiety of soluble guanylate cyclase (sGC), stimulating the synthesis of the diffusible second messenger guanosine 3Ј5Ј-cyclic monophosphate (cGMP) (6). The sGC/cGMP pathway plays a critical role in mediating the effects of CO on vascular relaxation and inhibition of platelet aggregation and coagulation (7,8).A recently recognized property of NO is its cell typespecific facilitation or inhibition of cell migration (9), a complex process involving molecular-...

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“…Conclusion medications such a s erythropoietin, oestrogen, phosphodiesterase-5 inhibitor, puerarin and Ginkgo biloba have been shown to augment EPC number and function in a non-diabetic settings (179). These factors, however, have not been studied in the setting of diabetes but may b e beneficial for therapeutic neovascularization in DM.…”

Section: Epc Transplantation In Diabetesmentioning

confidence: 99%

Endothelial Progenitor Cells in Diabetic Vasculopathy

Meiliana

Wijaya

2009

Indones Biomed J

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BACKGROUND: The discovery of endothelial progenitor cell (EPC) a decade ago by Asahara, et al has refuted the previous belief that vasculogenesis only occurs during embryogenesis. The reduced circulating concentration of EPCs is a surrogate marker of endothelial function and has been implicated in the pathogenesis of many vascular diseases.CONTENT: Diabetes is linked to impaired vascular function, including alterations in both endothelial cells and EPCs. A number of studies have shown that individuals with diabetes have decreased level of circulating EPCs and that the severity of disease is inversely proportional to EPC levels. In vitro, hyperglycemia increases the rate of EPC senescence and the angiogenic function of EPCs from patients with either type 1 or type 2 diabetes is impaired such that they are poorly proliferative and fail to incorporate into forming vessel-like structures. Given the comprehensive role of EPC alterations in diabetes complications, modulation of the levels and/or function of EPCs may be considered a potential therapeutic strategy.SUMMARY: The available data demonstrating that decrease or dysfunction of EPCs may have a prominent role in the pathogenesis of all diabetes complications. Further approaches, such as EPC administration, may represent novel treatments for diabetic vasculopathy in the future. To date, many barriers remain to such a therapeutic approach. Firstly, there is no specific marker for EPC at present. Secondly, techniques of EPC isolation are not standardized, preventing direct comparison between various studies. The long-term effects of transplanted EPCs are currently unknown.

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Endothelial progenitor cells: diagnostic and therapeutic considerations

Cited by 85 publications

References 99 publications

Circulating endothelial progenitor cells and depression: a possible novel link between heart and soul

Circulating endothelial progenitor cells and depression: a possible novel link between heart and soul

Carbon Monoxide and Nitric Oxide Mediate Cytoskeletal Reorganization in Microvascular Cells via Vasodilator-Stimulated Phosphoprotein Phosphorylation

Endothelial Progenitor Cells in Diabetic Vasculopathy

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