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Circulating microparticles from Crohn's disease patients cause endothelial and vascular dysfunctions.

Leonetti D, Reimund JM, Tesse A, Viennot S, Martinez MC, Bretagne AL, Andriantsitohaina R - PLoS ONE (2013)

Bottom Line: Circulating MP levels did not differ between HS and inactive CD patients except for an increase in leukocyte-derived MPs in CD.A significant correlation was found between total levels of MPs, those from platelets and endothelial cells, and the Harvey-Bradshaw clinical activity index.CDMPs induced vascular hypo-reactivity in aorta that was prevented by a nitric oxide (NO)-synthase inhibitor, and was associated with a subtle alteration of the balance between NO, reactive oxygen species and the release of COX metabolites.

View Article: PubMed Central - PubMed

Affiliation: LUNAM Université, Angers, France ; INSERM, U1063, Angers, France.

ABSTRACT

Background: Microparticles (MPs) are small vesicles released during cell activation or apoptosis. They are involved in coagulation, inflammation and vascular dysfunction in several diseases. We characterized circulating MPs from Crohn's Disease (CD) patients and evaluated their effects on endothelial function and vascular reactivity after in vivo injection into mice.

Methods: Circulating MPs and their cellular origins were examined by flow cytometry from blood samples from healthy subjects (HS) and inactive or active CD patients. MPs were intravenously injected into mice. After 24 hours, endothelial function and vascular reactivity were assessed.

Results: Circulating MP levels did not differ between HS and inactive CD patients except for an increase in leukocyte-derived MPs in CD. Active CD patients compared to HS displayed increased total circulating MPs, pro-coagulant MPs and those from platelets, endothelium, erythrocytes, leukocytes, activated leukocytes and activated platelets. A significant correlation was found between total levels of MPs, those from platelets and endothelial cells, and the Harvey-Bradshaw clinical activity index. MPs from CD, but not from HS, impaired endothelium-dependent relaxation in mice aorta and flow-induced dilation in mice small mesenteric arteries, MPs from inactive CD patients being more effective than those from active patients. CDMPs induced vascular hypo-reactivity in aorta that was prevented by a nitric oxide (NO)-synthase inhibitor, and was associated with a subtle alteration of the balance between NO, reactive oxygen species and the release of COX metabolites.

Conclusions: We provide evidence that MPs from CD patients significantly alter endothelial and vascular function and therefore, may play a role in CD pathophysiology, at least by contributing to uncontrolled vascular-dependent intestinal damage.

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Related in: MedlinePlus

Circulating microparticles (MPs) from healthy subjects (HS) (A) and Crohn’s disease (CD) patients (B) and Flowcount beads (Beads region, 10 µm diameter) are visualized in a side scatter (SS)/forward scatter (FS) logarithmic representation.MPs are defined as events with size 0.1 to 1 µm gated in the “MPs” window. Circulating MP levels in patients with inactive CD and active CD compared to HS. Total circulating MPs (C), CD41+ MPs (D), annexin V+ MPs (E), CD146+ MPs (F), CD45+ and CD235a+ MPs (G), CD62L+ and CD62P+ MPs (H). MPs from HS (n = 28), MPs from inactive CD patients (inactive CD n = 13) and MPs from active CD patients (active CD n = 26). Results are expressed as events/µL of plasma and given as mean ± SEM. *p<0.05, ***p<0.001 vs HS; †p<0.05, ††p<0.01 active CD vs inactive CD.
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pone-0073088-g001: Circulating microparticles (MPs) from healthy subjects (HS) (A) and Crohn’s disease (CD) patients (B) and Flowcount beads (Beads region, 10 µm diameter) are visualized in a side scatter (SS)/forward scatter (FS) logarithmic representation.MPs are defined as events with size 0.1 to 1 µm gated in the “MPs” window. Circulating MP levels in patients with inactive CD and active CD compared to HS. Total circulating MPs (C), CD41+ MPs (D), annexin V+ MPs (E), CD146+ MPs (F), CD45+ and CD235a+ MPs (G), CD62L+ and CD62P+ MPs (H). MPs from HS (n = 28), MPs from inactive CD patients (inactive CD n = 13) and MPs from active CD patients (active CD n = 26). Results are expressed as events/µL of plasma and given as mean ± SEM. *p<0.05, ***p<0.001 vs HS; †p<0.05, ††p<0.01 active CD vs inactive CD.

Mentions: The total number of circulating MPs was significantly increased in active CD patients compared with HS and inactive CD patients (Figure 1C). Phenotypical characterisation of cellular origin of MPs from HS and inactive CD patients did not show significant difference between the two groups except that of leukocytes (CD45+) MPs (Figure 1D–1H). Interestingly, compared to HS, active CD patients displayed increases of pro-coagulant (annexing V+) MPs and those from platelets (CD41+), endothelial cells (CD146+), leukocytes (CD45+), erythrocytes (CD235a+), activated leukocytes (CD62L+) and activated platelets (CD62P+) (Figure 1D–1H). MPs from macrophages (CD11b+) and granulocytes (CD66b+) were not significantly different between HS and active CD patients (not shown). Finally, active CD patients showed increased total circulating MPs, platelet- and endothelial-derived MPs when compared to inactive patients (Figure 1C, 1D and 1F).


Circulating microparticles from Crohn's disease patients cause endothelial and vascular dysfunctions.

Leonetti D, Reimund JM, Tesse A, Viennot S, Martinez MC, Bretagne AL, Andriantsitohaina R - PLoS ONE (2013)

Circulating microparticles (MPs) from healthy subjects (HS) (A) and Crohn’s disease (CD) patients (B) and Flowcount beads (Beads region, 10 µm diameter) are visualized in a side scatter (SS)/forward scatter (FS) logarithmic representation.MPs are defined as events with size 0.1 to 1 µm gated in the “MPs” window. Circulating MP levels in patients with inactive CD and active CD compared to HS. Total circulating MPs (C), CD41+ MPs (D), annexin V+ MPs (E), CD146+ MPs (F), CD45+ and CD235a+ MPs (G), CD62L+ and CD62P+ MPs (H). MPs from HS (n = 28), MPs from inactive CD patients (inactive CD n = 13) and MPs from active CD patients (active CD n = 26). Results are expressed as events/µL of plasma and given as mean ± SEM. *p<0.05, ***p<0.001 vs HS; †p<0.05, ††p<0.01 active CD vs inactive CD.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3760904&req=5

pone-0073088-g001: Circulating microparticles (MPs) from healthy subjects (HS) (A) and Crohn’s disease (CD) patients (B) and Flowcount beads (Beads region, 10 µm diameter) are visualized in a side scatter (SS)/forward scatter (FS) logarithmic representation.MPs are defined as events with size 0.1 to 1 µm gated in the “MPs” window. Circulating MP levels in patients with inactive CD and active CD compared to HS. Total circulating MPs (C), CD41+ MPs (D), annexin V+ MPs (E), CD146+ MPs (F), CD45+ and CD235a+ MPs (G), CD62L+ and CD62P+ MPs (H). MPs from HS (n = 28), MPs from inactive CD patients (inactive CD n = 13) and MPs from active CD patients (active CD n = 26). Results are expressed as events/µL of plasma and given as mean ± SEM. *p<0.05, ***p<0.001 vs HS; †p<0.05, ††p<0.01 active CD vs inactive CD.
Mentions: The total number of circulating MPs was significantly increased in active CD patients compared with HS and inactive CD patients (Figure 1C). Phenotypical characterisation of cellular origin of MPs from HS and inactive CD patients did not show significant difference between the two groups except that of leukocytes (CD45+) MPs (Figure 1D–1H). Interestingly, compared to HS, active CD patients displayed increases of pro-coagulant (annexing V+) MPs and those from platelets (CD41+), endothelial cells (CD146+), leukocytes (CD45+), erythrocytes (CD235a+), activated leukocytes (CD62L+) and activated platelets (CD62P+) (Figure 1D–1H). MPs from macrophages (CD11b+) and granulocytes (CD66b+) were not significantly different between HS and active CD patients (not shown). Finally, active CD patients showed increased total circulating MPs, platelet- and endothelial-derived MPs when compared to inactive patients (Figure 1C, 1D and 1F).

Bottom Line: Circulating MP levels did not differ between HS and inactive CD patients except for an increase in leukocyte-derived MPs in CD.A significant correlation was found between total levels of MPs, those from platelets and endothelial cells, and the Harvey-Bradshaw clinical activity index.CDMPs induced vascular hypo-reactivity in aorta that was prevented by a nitric oxide (NO)-synthase inhibitor, and was associated with a subtle alteration of the balance between NO, reactive oxygen species and the release of COX metabolites.

View Article: PubMed Central - PubMed

Affiliation: LUNAM Université, Angers, France ; INSERM, U1063, Angers, France.

ABSTRACT

Background: Microparticles (MPs) are small vesicles released during cell activation or apoptosis. They are involved in coagulation, inflammation and vascular dysfunction in several diseases. We characterized circulating MPs from Crohn's Disease (CD) patients and evaluated their effects on endothelial function and vascular reactivity after in vivo injection into mice.

Methods: Circulating MPs and their cellular origins were examined by flow cytometry from blood samples from healthy subjects (HS) and inactive or active CD patients. MPs were intravenously injected into mice. After 24 hours, endothelial function and vascular reactivity were assessed.

Results: Circulating MP levels did not differ between HS and inactive CD patients except for an increase in leukocyte-derived MPs in CD. Active CD patients compared to HS displayed increased total circulating MPs, pro-coagulant MPs and those from platelets, endothelium, erythrocytes, leukocytes, activated leukocytes and activated platelets. A significant correlation was found between total levels of MPs, those from platelets and endothelial cells, and the Harvey-Bradshaw clinical activity index. MPs from CD, but not from HS, impaired endothelium-dependent relaxation in mice aorta and flow-induced dilation in mice small mesenteric arteries, MPs from inactive CD patients being more effective than those from active patients. CDMPs induced vascular hypo-reactivity in aorta that was prevented by a nitric oxide (NO)-synthase inhibitor, and was associated with a subtle alteration of the balance between NO, reactive oxygen species and the release of COX metabolites.

Conclusions: We provide evidence that MPs from CD patients significantly alter endothelial and vascular function and therefore, may play a role in CD pathophysiology, at least by contributing to uncontrolled vascular-dependent intestinal damage.

Show MeSH
Related in: MedlinePlus