Transgenic sickle mice have vascular inflammation

Belcher, John D.; Bryant, Christopher; Nguyen, Julia; Bowlin, Paul R.; Kielbik, Miroslaw C.; Bischof, John C.; Hebbel, Robert P.; Vercellotti, Gregory M.

doi:10.1182/blood-2002-10-3313

Cited by 210 publications

(206 citation statements)

References 72 publications

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“…Endothelial cells (ECs) can detach from the vascular wall and circulate in the bloodstream, and would then be termed CECs. It has long been shown that the level of CECs is significantly higher in patients with widespread vascular damage, such as antineutrophil cytoplasmic antibody‐associated small vessel vasculitis (Woywodt, Streiber, et al., 2003), sickle cell crisis (Belcher et al., 2003), and pulmonary hypertension (Bull et al., 2003). Therefore, CECs have been used as a marker of endothelial damage in a variety of vascular disorders (Alessio et al., 2013; Davignon & Ganz, 2004; Dignat‐George & Sampol, 2000).…”

Section: Discussionmentioning

confidence: 99%

Circulating endothelial progenitor cells and endothelial cells in moyamoya disease

et al. 2018

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IntroductionThere is no well‐recognized biomarker for accurately predicting outcome in the presence of moyamoya disease (MMD), a progressive occlusive cerebrovascular disease of the internal carotid arteries or their branches. The aim of this study was to investigate the presence of endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) in MMD and correlate the findings with clinical features.MethodsPatients with MMD (n = 66) were compared with healthy controls (n = 81). Blood samples were obtained from an antecubital vein and analyzed using flow cytometry. EPCs were defined as CD31+ CD45dim CD34br CD133+ and CECs as CD31br CD45− CD34dim CD133−. Univariate and multivariate linear regression analyses were carried out.ResultsThe CEC counts were significantly higher in the patients than in the controls (p = 0.008). In multivariate analysis, EPC counts were independently associated with age of patients with MMD (p = 0.049) and CEC counts were independently negatively associated with concomitant disease such as hypertension, diabetes mellitus, and coronary heart disease (p = 0.034).ConclusionsThis is the first study to investigate the presence of CECs in the plasma of patients with MMD, and the amount of CECs was negatively correlated with concomitant disease in these patients.

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Section: Discussionmentioning

confidence: 99%

Circulating endothelial progenitor cells and endothelial cells in moyamoya disease

et al. 2018

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“…Upon pathological analysis, there is tissue damage in multiple organs including the kidney, liver, lung, and spleen [34][35][36]. Like human SCD patients, transgenic b S mice display numerous signs of an inflammatory response such as elevated white counts and enhanced activation of NF-kB, a transcription factor critical for the inflammatory response [37]. In addition, there are significant increases in the expression of endothelial cell adhesion molecules and the acute phase response protein serum amyloid P-component (SAP) [37].…”

Section: Introductionmentioning

confidence: 99%

“…Like human SCD patients, transgenic b S mice display numerous signs of an inflammatory response such as elevated white counts and enhanced activation of NF-kB, a transcription factor critical for the inflammatory response [37]. In addition, there are significant increases in the expression of endothelial cell adhesion molecules and the acute phase response protein serum amyloid P-component (SAP) [37]. Sickle mice exhibit biochemical footprints consistent with excessive reactive oxygen species (ROS) generation, even at ambient air [5].…”

Section: Introductionmentioning

confidence: 99%

Microvascular blood flow and stasis in transgenic sickle mice: Utility of a dorsal skin fold chamber for intravital microscopy

et al. 2004

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Vascular inflammation, secondary to ischemia-reperfusion injury, may play an essential role in vaso-occlusion in sickle cell disease (SCD). To investigate this hypothesis, dorsal skin fold chambers (DSFCs) were implanted on normal and transgenic sickle mice expressing human a and b s /b s-Antilles globin chains. Microvessels in the DSFC were visualized by intravital microscopy at baseline in ambient air and after exposure to hypoxia-reoxygenation. The mean venule diameter decreased 9% (P < 0.01) in sickle mice after hypoxia-reoxygenation but remained constant in normal mice. The mean RBC velocity and wall shear rate decreased 55% (P < 0.001) in sickle but not normal mice after hypoxia-reoxygenation. None of the venules in normal mice became static at any time during hypoxia-reoxygenation; however, after 1 hr of hypoxia and 1 hr of reoxygenation, 11.9% of the venules in sickle mice became static (P < 0.001). After 1 hr of hypoxia and 4 hr of reoxygenation, most of the stasis had resolved; only 3.6% of the subcutaneous venules in sickle mice remained static (P = 0.01). All of the venules were flowing again after 24 hr of reoxygenation. Vascular stasis could not be induced in the subcutaneous venules of sickle mice by tumor necrosis factor alpha (TNF-a). Leukocyte rolling flux and firm adhesion, manifestations of vascular inflammation, were significantly higher at baseline in sickle mice compared to normal (P < 0.01) and increased 3-fold in sickle (P < 0.01), but not in normal mice, after hypoxia-reoxygenation. Plugs of adherent leukocytes were seen at bifurcations at the beginning of static venules. Misshapen RBCs were also seen in subcutaneous venules. Am.

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“…Elsewhere, we have unambiguously demonstrated that this TF expression mouse is triggered by the inflammatory state that is known to develop in the NY1DD mouse on exposure to H/R [6]. We believe that the documented presence of an inflammatory state in the hBERK1 mouse [8] also possibly accounts for its TF expression even at ambient air, although this has not been unambiguously proven. In any case, we had expected the hypothesis stated above to be true because a TF-modulating effect for NO has already been demonstrated in cultured endothelial cells [9,10].…”

Section: Discussionmentioning

confidence: 81%

“…This observation is relevant because human and murine sickle states are both characterized by this state [7,8]. Indeed, we regard sickle disease as comprising a paradigmatic example of ischemia/reperfusion [7].…”

Section: Introductionmentioning

confidence: 99%

Endothelial nitric oxide synthase and nitric oxide regulate endothelial tissue factor expression in vivo in the sickle transgenic mouse

et al. 2009

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Activation of the coagulation system is a characteristic feature of sickle cell anemia, which also includes clinical thrombosis. The sickle transgenic mouse abnormally expresses tissue factor (TF) on the pulmonary vein endothelium. Knowing that this aberrancy is stimulated by inflammation, we sought to determine whether nitric oxide (NO) contributes to regulation of endothelial TF expression in the sickle mouse model. We used the NY1DD sickle mouse, which exhibits a low-TF to high-TF phenotype switch on exposure to hypoxia/reoxygenation. Manipulations of NO biology, such as breathing NO or addition of arginine or L-NAME (N-nitro-L-arginine-methyl-ester) to the diet, caused significant modulations of TF expression. This was also seen in hBERK1 sickle mice, which have a different genetic background and already have high-TF even at ambient air. Study of NY1DD animals bred to overexpress endothelial nitric oxide synthase (eNOS; eNOSTg) or to have an eNOS knockout state (one eNOS 2/2 animal and several eNOS 1/2 animals) demonstrated that eNOS modulates endothelial TF expression in vivo by down-regulating it. Thus, the biodeficiency of NO characteristic of patients with sickle cell anemia may heighten risk for activation of the coagulation system. Am. J. Hematol. 85:41-45, 2010. V

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Transgenic sickle mice have vascular inflammation

Cited by 210 publications

References 72 publications

Circulating endothelial progenitor cells and endothelial cells in moyamoya disease

Circulating endothelial progenitor cells and endothelial cells in moyamoya disease

Microvascular blood flow and stasis in transgenic sickle mice: Utility of a dorsal skin fold chamber for intravital microscopy

Endothelial nitric oxide synthase and nitric oxide regulate endothelial tissue factor expression in vivo in the sickle transgenic mouse

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