title: Endothelial dysfunction caused by circulating microparticles from patients with metabolic syndrome.
abstract: Microparticles are membrane vesicles that are released during cell activation and apoptosis. Elevated levels of microparticles occur in many cardiovascular diseases; therefore, we characterized circulating microparticles from both metabolic syndrome (MS) patients and healthy patients. We evaluated microparticle effects on endothelial function; however, links between circulating microparticles and endothelial dysfunction have not yet been demonstrated. Circulating microparticles and their cellular origins were examined by flow cytometry of blood samples from patients and healthy subjects. Microparticles were used either to treat human endothelial cells in vitro or to assess endothelium function in mice after intravenous injection. MS patients had increased circulating levels of microparticles compared with healthy patients, including microparticles from platelet, endothelial, erythrocyte, and procoagulant origins. In vitro treatment of endothelial cells with microparticles from MS patients reduced both nitric oxide (NO) and superoxide anion production, resulting in protein tyrosine nitration. These effects were associated with enhanced phosphorylation of endothelial NO synthase at the site of inhibition. The reduction of O2(-) was linked to both reduced expression of p47 phox of NADPH oxidase and overexpression of extracellular superoxide dismutase. The decrease in NO production was triggered by nonplatelet-derived microparticles. In vivo injection of MS microparticles into mice impaired endothelium-dependent relaxation and decreased endothelial NO synthase expression. These data provide evidence that circulating microparticles from MS patients influence endothelial dysfunction.
authors.affiliation: INSERM U771, Centre National de la Recherche Scientifique Unité Mixte de Recherche, 6214, the Université d'Angers, Angers, France.
authors.forename: Abdelali
authors.initials: A
authors.lastname: Agouni
authors.forename: Anne Hélène
authors.initials: AH
authors.lastname: Lagrue-Lak-Hal
authors.forename: Pierre Henri
authors.initials: PH
authors.lastname: Ducluzeau
authors.forename: Hadj Ahmed
authors.initials: HA
authors.lastname: Mostefai
authors.forename: Catherine
authors.initials: C
authors.lastname: Draunet-Busson
authors.forename: Georges
authors.initials: G
authors.lastname: Leftheriotis
authors.forename: Christophe
authors.initials: C
authors.lastname: Heymes
authors.forename: Maria Carmen
authors.initials: MC
authors.lastname: Martinez
authors.forename: Ramaroson
authors.initials: R
authors.lastname: Andriantsitohaina
mesh_terms: D000818:Animals; D001011:Aorta / Q000503:physiopathology; D001792:Blood Platelets / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000201:enzymology / Q000378:metabolism; D004730:Endothelium, Vascular / Q000201:enzymology / Q000503:physiopathology*; D005260:Female; D005786:Gene Expression Regulation; D006262:Health; D006801:Humans; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000201:enzymology / Q000503:physiopathology*; D051379:Mice; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D022161:Transport Vesicles / Q000378:metabolism*; D014664:Vasodilation
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D012333:RNA, Messenger; D013481:Superoxides; D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III
references.citation: Endocr Metab Immune Disord Drug Targets. 2006 Sep;6(3):287-94
references.pmid: 17017980
references.citation: J Clin Invest. 1998 Jul 1;102(1):136-44
references.pmid: 9649567
references.citation: J Immunol. 2008 Apr 1;180(7):5028-35
references.pmid: 18354228
references.citation: J Am Soc Nephrol. 2005 Nov;16(11):3381-8
references.pmid: 16192427
references.citation: J Clin Endocrinol Metab. 2006 Sep;91(9):3676-9
references.pmid: 16822816
references.citation: Ann Med. 2006;38(1):34-41
references.pmid: 16448987
references.citation: Gastroenterology. 2000 Jul;119(1):201-10
references.pmid: 10889170
references.citation: Circulation. 2005 Nov 15;112(20):3066-72
references.pmid: 16275870
references.citation: Am J Physiol Heart Circ Physiol. 2004 May;286(5):H1910-5
references.pmid: 15072974
references.citation: Arterioscler Thromb Vasc Biol. 2006 Dec;26(12):2775-80
references.pmid: 17038634
references.citation: Genome Biol. 2002 Jun 18;3(7):RESEARCH0034
references.pmid: 12184808
references.citation: Best Pract Res Clin Endocrinol Metab. 2006 Dec;20(4):665-79
references.pmid: 17161338
references.citation: Circulation. 2004 Sep 7;110(10):1245-50
references.pmid: 15326067
references.citation: J Clin Invest. 1997 May 1;99(9):2118-27
references.pmid: 9151784
references.citation: Nature. 2001 Dec 13;414(6865):782-7
references.pmid: 11742409
references.citation: Physiology (Bethesda). 2005 Feb;20:22-7
references.pmid: 15653836
references.citation: Blood. 2000 Feb 1;95(3):930-5
references.pmid: 10648405
references.citation: Diabetes. 2002 Sep;51(9):2840-5
references.pmid: 12196479
references.citation: J Pharmacol Exp Ther. 2008 Feb;324(2):539-47
references.pmid: 18039959
references.citation: Am J Cardiol. 2006 Jul 1;98(1):70-4
references.pmid: 16784924
references.citation: Diabetes Care. 2005 Nov;28(11):2745-9
references.pmid: 16249550
references.citation: Med J Aust. 2006 Oct 16;185(8):445-9
references.pmid: 17137436
references.citation: Dig Dis Sci. 2005 Mar;50(3):574-80
references.pmid: 15810645
references.citation: J Biol Chem. 1999 Aug 13;274(33):23111-8
references.pmid: 10438480
references.citation: Pathol Biol (Paris). 2006 Sep;54(7):375-86
references.pmid: 16904849
references.citation: Am J Physiol Gastrointest Liver Physiol. 2001 Jan;280(1):G68-74
references.pmid: 11123199
references.citation: Shock. 2006 Nov;26(5):464-71
references.pmid: 17047516
references.citation: Diabetes Metab. 2006 Feb;32(1):82-5
references.pmid: 16523191
references.citation: J Am Coll Cardiol. 2005 May 3;45(9):1467-71
references.pmid: 15862420
references.citation: Thromb Haemost. 2004 Apr;91(4):667-73
references.pmid: 15045126
references.citation: Am J Pathol. 2006 Oct;169(4):1473-83
references.pmid: 17003500
references.citation: Circulation. 2000 Feb 29;101(8):841-3
references.pmid: 10694520
references.citation: Circulation. 2002 Nov 5;106(19):2442-7
references.pmid: 12417540
references.citation: J Trauma. 2004 Apr;56(4):823-30; discussion 830-1
references.pmid: 15187749
references.citation: Clin Exp Pharmacol Physiol. 2007 Sep;34(9):933-7
references.pmid: 17645643
references.citation: Lancet. 2005 Apr 16-22;365(9468):1415-28
references.pmid: 15836891
references.citation: FASEB J. 2007 Sep;21(11):2735-41
references.pmid: 17428963
references.citation: Am J Obstet Gynecol. 2004 Oct;191(4):1418-24
references.pmid: 15507976
references.citation: Am J Physiol Heart Circ Physiol. 2005 Mar;288(3):H1004-9
references.pmid: 15706036