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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 impair endothelium-dependent relaxation in mouse aorta.Acetylcholine (Ach)-induced relaxation 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). Results are expressed as a percentage of U46619-induced pre-contraction and given as mean ± SEM (n = 5–11). ***p<0.001 vs CTL; †††p<0.001 vs HSMPs; $$$p<0.001 active CDMPs vs inactive CDMPs.
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pone-0073088-g003: Microparticles (MPs) from CD patients impair endothelium-dependent relaxation in mouse aorta.Acetylcholine (Ach)-induced relaxation in aortic rings isolated from mice injected in vivo with vehicle (controls (CTL)), MPs from HS (HSMPs) and MPs from CD patients (CDMPs) (A) subsequently separated in inactive CD patients (inactive CDMPs) (B) and active CD patients (active CDMPs) (B). Results are expressed as a percentage of U46619-induced pre-contraction and given as mean ± SEM (n = 5–11). ***p<0.001 vs CTL; †††p<0.001 vs HSMPs; $$$p<0.001 active CDMPs vs inactive CDMPs.

Mentions: The endothelium-dependent relaxation to acetylcholine was significantly impaired in aorta isolated from mice injected with CDMPs compared to aorta isolated from mice injected either with vehicle or with HSMPs (Emax: 69.3±2.1%, 65.2±2% and 45.1±1.02% for CTL, HSMPS and CDMPs, respectively p<0.001) (Figure 3A). Injection of either inactive or active CDMPs reduced acetylcholine-induced aortic endothelium-dependent relaxation when compared to those taken from HSMP-treated mice. Unexpectedly, inactive CDMPs were more effective than active CDMPs in impairing endothelial function (Emax inactive CDMPs 41.2±1.3%; Emax active CDMPs 49.8±1.03%; p<0.01) (Figure 3B).


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 impair endothelium-dependent relaxation in mouse aorta.Acetylcholine (Ach)-induced relaxation 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). Results are expressed as a percentage of U46619-induced pre-contraction and given as mean ± SEM (n = 5–11). ***p<0.001 vs CTL; †††p<0.001 vs HSMPs; $$$p<0.001 active CDMPs vs inactive CDMPs.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3760904&req=5

pone-0073088-g003: Microparticles (MPs) from CD patients impair endothelium-dependent relaxation in mouse aorta.Acetylcholine (Ach)-induced relaxation 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). Results are expressed as a percentage of U46619-induced pre-contraction and given as mean ± SEM (n = 5–11). ***p<0.001 vs CTL; †††p<0.001 vs HSMPs; $$$p<0.001 active CDMPs vs inactive CDMPs.
Mentions: The endothelium-dependent relaxation to acetylcholine was significantly impaired in aorta isolated from mice injected with CDMPs compared to aorta isolated from mice injected either with vehicle or with HSMPs (Emax: 69.3±2.1%, 65.2±2% and 45.1±1.02% for CTL, HSMPS and CDMPs, respectively p<0.001) (Figure 3A). Injection of either inactive or active CDMPs reduced acetylcholine-induced aortic endothelium-dependent relaxation when compared to those taken from HSMP-treated mice. Unexpectedly, inactive CDMPs were more effective than active CDMPs in impairing endothelial function (Emax inactive CDMPs 41.2±1.3%; Emax active CDMPs 49.8±1.03%; p<0.01) (Figure 3B).

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