Circulating Endothelial Progenitor Cells in Patients with ANCA-Associated Vasculitis

Závada, Jakub; Kideryová, L; Pytlík, Robert; Vankova, Zdenka; Tesař, Vladimı́r

doi:10.1159/000142690

Cited by 23 publications

(12 citation statements)

References 31 publications

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“…The results of our study differed from previous studies [ 25 – 27 ]. In an earlier study by de Groot et al, AAV patients and HC showed no difference in hematopoietic stem cell numbers [ 26 ].…”

Section: Discussioncontrasting

confidence: 99%

Endothelial progenitor cells are differentially impaired in ANCA-associated vasculitis compared to healthy controls

et al. 2016

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BackgroundEndothelial progenitor cells (EPC) are of major importance in vascular repair under healthy circumstances. Vascular injury in need of repair occurs frequently in ANCA-associated vasculitis (AAV). A specialized T cell subset enhancing EPC function and differentiation has recently been described. These angiogenic T cells (Tang) may have an important impact on the vascular repair process. Therefore, the aim of our study was to investigate EPC and Tang in AAV.MethodsFifty-three patients suffering from AAV and 29 healthy controls (HC) were enrolled in our study. Forty-four patients were in remission, nine patients were in active state of disease. Patients were either untreated or were under monotherapy with low-dose steroids (max. 5 mg/day) at the time of sampling. Circulating EPC and Tang were determined by flow cytometry (FACS). The functional capacity of EPC was assessed by established cell culture methods.ResultsCirculating EPC were significantly decreased in AAV as compared to HC. The capacity of EPC to differentiate and proliferate was differentially impaired in patients as compared to HC. The outgrowth of endothelial colony-forming cells (ECFC) was severely decreased in patients whereas colony-forming units-endothelial cell (CFU-EC) outgrowth was unaffected. ECFC and CFU-EC differentiation was strictly T cell-dependent. Patients with a relapsing disease course had an impaired ECFC outgrowth and expansion of Tang as compared to patients with a stable, nonrelapsing disease.ConclusionsThe differentiation process of EPC is impaired in AAV. This may favor insufficient vascular repair promoting a relapsing disease course. Finally, these factors may explain a higher cardiovascular morbidity as has been previously documented in AAV.

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Section: Discussioncontrasting

confidence: 99%

Endothelial progenitor cells are differentially impaired in ANCA-associated vasculitis compared to healthy controls

et al. 2016

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“…In addition, GPA and MPA patients displayed lower proliferative activity of blood-derived eEOCs (lower numbers of colonies formed in culture—CFU assay). This was in line with observations made by Závada and colleagues [14] who showed significantly decreased CFU-ECs (colony-forming unit endothelial cells) in patients with ANCA-associated vasculitis (AAV). The lower percentages of Flk-1 + myelomonocytic cells despite physiological levels of CD133 + /Flk-1 + myelomonocytic cells might result from a general defect of endothelial differentiation which possibly not only involves de novo generation of eEOCs in the bone marrow but also further differentiation of circulating CD133 + /Flk-1 + cells into Flk-1 + myelomonocytic cells.…”

Section: Discussionsupporting

confidence: 92%

“…The fact that eEOC regeneration is impaired in GPA (and MPA) patients, an observation also made by other investigators [14], combined with the apparently increased antibody binding to PR3 in cells with endothelial properties potentially indicates a pathophysiological role for proteinase 3 in mediating suppression of endothelial-type cells.…”

Section: Discussionsupporting

confidence: 59%

“…A recent study also showed a significant and persistent deficiency of circulating EPCs (eEOCs) in patients with AAV. The authors concluded that low EPC numbers could potentially reflect an impaired mechanism of vascular repair and may contribute to repeated relapses of the disease [14]. In GPA and MPA, antibodies directed againts PR3 and MPO have become important tools in diagnosing the diseases and in monitoring disease activities under treatment [15].…”

Section: Introductionmentioning

confidence: 99%

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Impairment and Differential Expression of PR3 and MPO on Peripheral Myelomonocytic Cells with Endothelial Properties in Granulomatosis with Polyangiitis

Patschan

Henze

et al. 2012

International Journal of Nephrology

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Background. Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are autoimmune-mediated diseases characterized by vasculitic inflammation of respiratory tract and kidneys. Clinical observations indicated a strong association between disease activity and serum levels of certain types of autoantibodies (antineutrophil cytoplasm antibodies with cytoplasmic [cANCA in GPA] or perinuclear [pAN CA in MPA] immunofluorescence). Pathologically, both diseases are characterized by severe microvascular endothelial cell damage. Early endothelial outgrowth cells (eEOCs) have been shown to be critically involved in neovascularization under both physiological and pathological condition.Objectives. The principal aims of our study were (i) to analyze the regenerative activity of the eEOC system and (ii) to determine mPR3 and MPO expression in myelo monocytic cells with endothelial characteristics in GPA and MPA patients.Methods. In 27 GPA and 10 MPA patients, regenerative activity blood-derived eEOCs were analyzed using a culture-forming assay. Flk-1+, CD133+/Flk-1+, mPR3+, and Flk-1+/mPR3+myelomonocytic cells were quantified by FACS analysis. Serum levels of Angiopoietin-1 and TNF-αwere measured by ELISA.Results. We found reduced eEOC regeneration, accompanied by lower serum levels of Angiopoietin-1 in GPA patients as compared to healthy controls. In addition, the total numbers of Flk-1+myelomonocytic cells in the peripheral circulation were decreased. Membrane PR3 expression was significantly higher in total as well as in Flk-1+myelomonocytic cells. Expression of MPO was not different between the groups.Conclusions. These data suggest impairment of the eEOC system and a possible role for PR3 in this process in patients suffering from GPA.

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“…Both these EPC parameters, however, increased after the institution of immunosuppressive therapy and disease remission in GPA patients. Závada et al confirmed the observation of Holmen et al of low EPC-CFU in adults with AAV, particularly in uraemic patients; but in contrast to the study of de Groot et al found that neither institution of treatment nor entering remission increased the number of EPC-CFU [ 47 ]. In a separate study the same group went on to demonstrate that patients with AAV who had low EPC-CFU at first presentation had significantly higher rates of early disease relapse, for the first time suggesting that EPC levels might be important prognostically in AAV [ 48 ].…”

Section: Discussionmentioning

confidence: 75%

Impaired function of endothelial progenitor cells in children with primary systemic vasculitis

Hong¹,

Eleftheriou²,

Klein³

et al. 2015

Arthritis Res Ther

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IntroductionPreviously, we demonstrated that children with active systemic vasculitis (SV) have higher circulating CD34 + CD133 + KDR+ endothelial progenitor cells (EPC); the function of these EPCs, and their relationship with disease activity in vasculitis remains largely unexplored. We hypothesized that although EPC numbers are higher, EPC function is impaired in active SV of the young. The aims of this study were therefore to: 1. investigate the relationship between disease activity and EPC function in children with SV; and 2. study the influence of systemic inflammation on EPC function by investigating the effects of hyperthermia and TNF-α on EPC function.MethodsWe performed a cross-sectional study of unselected children with SV with different levels of disease activity attending a single center (Great Ormond Street Hospital, London) between October 2008 and December 2014. EPCs were isolated from peripheral blood of children with SV, and healthy child controls. EPC function was assessed by their potential to form colonies (EPC-CFU), and ability to form clusters and incorporate into human umbilical vein endothelial cell (HUVEC) vascular structures in matrigel. The effects of hyperthermia and TNF-α on EPC function were also studied.ResultsTwenty children, median age 12-years (5–16.5; nine males) were studied. EPC-CFU and the number of EPC clusters formed on matrigel were significantly reduced in children with active vasculitis compared with healthy controls (p = 0.02 for EPC-CFU; p = 0.01 for EPC cluster formation). Those with active vasculitis had lower EPC-CFU and EPC cluster formation than those with inactive disease, although non-significantly so. In addition, EPC incorporation into matrigel HUVEC networks was lower in children with SV compared with healthy children, irrespective of disease activity. Ex-vivo pre-treatment of EPC with hyperthermia impaired EPC function; TNF-α down-regulated EPC expression of CD18/CD11b and resulted in decreased incorporation into HUVEC networks.ConclusionsWhilst our previous work showed that circulating CD34 + EPC numbers are well preserved, this study revealed that EPC function is significantly impaired in children with vasculitis. It is possible that the chronic inflammatory milieu associated with vasculitis may impair EPC function, and thus contribute to an unfavourable balance between endothelial injury and repair. The mechanism of this remains to be established, however.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0810-3) contains supplementary material, which is available to authorized users.

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Circulating Endothelial Progenitor Cells in Patients with ANCA-Associated Vasculitis

Cited by 23 publications

References 31 publications

Endothelial progenitor cells are differentially impaired in ANCA-associated vasculitis compared to healthy controls

Endothelial progenitor cells are differentially impaired in ANCA-associated vasculitis compared to healthy controls

Impairment and Differential Expression of PR3 and MPO on Peripheral Myelomonocytic Cells with Endothelial Properties in Granulomatosis with Polyangiitis

Impaired function of endothelial progenitor cells in children with primary systemic vasculitis

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