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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

Microparticles (MPs) from CD patients decrease 5-HT contraction in mouse aorta.Concentration-effect curves in response to 5-HT in aortic rings isolated from mice injected in vivo with vehicle (controls (CTL)), MPs from HS (HSMPs) and MPs from CD patients (CDMPs) (A) subsequently separated in inactive CD patients (inactive CDMPs) (B) and active CD patients (active CDMPs) (B). Contraction are expressed in mN/mm. Results are given as mean ± SEM (n = 6–13). **p<0.01, ***p<0.001 vs CTL; ††p<0.001, †††p<0.001 vs HSMPs.
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pone-0073088-g005: Microparticles (MPs) from CD patients decrease 5-HT contraction in mouse aorta.Concentration-effect curves in response to 5-HT in aortic rings isolated from mice injected in vivo with vehicle (controls (CTL)), MPs from HS (HSMPs) and MPs from CD patients (CDMPs) (A) subsequently separated in inactive CD patients (inactive CDMPs) (B) and active CD patients (active CDMPs) (B). Contraction are expressed in mN/mm. Results are given as mean ± SEM (n = 6–13). **p<0.01, ***p<0.001 vs CTL; ††p<0.001, †††p<0.001 vs HSMPs.

Mentions: 5-HT produced a concentration-dependent increase in tension in aortic rings from all groups of mice; however, vascular reactivity to the agonist was markedly decreased in mice treated with CDMPs compared to those treated either with vehicle or HSMPs (Figure 5A). Both inactive and active CDMPs reduced vascular reactivity to 5-HT to the same extent when compared to vehicle or HSMPs (Figure 5B). Since no difference of hyporeactivity was observed between inactive and active CD patients, the mechanisms involved for this process was only investigated in vessels from mice treated with active CDMPs.


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)

Microparticles (MPs) from CD patients decrease 5-HT contraction in mouse aorta.Concentration-effect curves in response to 5-HT in aortic rings isolated from mice injected in vivo with vehicle (controls (CTL)), MPs from HS (HSMPs) and MPs from CD patients (CDMPs) (A) subsequently separated in inactive CD patients (inactive CDMPs) (B) and active CD patients (active CDMPs) (B). Contraction are expressed in mN/mm. Results are given as mean ± SEM (n = 6–13). **p<0.01, ***p<0.001 vs CTL; ††p<0.001, †††p<0.001 vs HSMPs.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0073088-g005: Microparticles (MPs) from CD patients decrease 5-HT contraction in mouse aorta.Concentration-effect curves in response to 5-HT in aortic rings isolated from mice injected in vivo with vehicle (controls (CTL)), MPs from HS (HSMPs) and MPs from CD patients (CDMPs) (A) subsequently separated in inactive CD patients (inactive CDMPs) (B) and active CD patients (active CDMPs) (B). Contraction are expressed in mN/mm. Results are given as mean ± SEM (n = 6–13). **p<0.01, ***p<0.001 vs CTL; ††p<0.001, †††p<0.001 vs HSMPs.
Mentions: 5-HT produced a concentration-dependent increase in tension in aortic rings from all groups of mice; however, vascular reactivity to the agonist was markedly decreased in mice treated with CDMPs compared to those treated either with vehicle or HSMPs (Figure 5A). Both inactive and active CDMPs reduced vascular reactivity to 5-HT to the same extent when compared to vehicle or HSMPs (Figure 5B). Since no difference of hyporeactivity was observed between inactive and active CD patients, the mechanisms involved for this process was only investigated in vessels from mice treated with active CDMPs.

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