Download PDF
Thromb Haemost 2008; 99(04): 711-719
DOI: 10.1160/TH07-05-0334
Platelets and Blood Cells
Schattauer GmbH

Increased levels of circulating microparticles in patients with severe aortic valve stenosis

Philipp Diehl   *
1   Department for Cardiology and Angiology
,
Ferenc Nagy   *
1   Department for Cardiology and Angiology
,
Verena Sossong
1   Department for Cardiology and Angiology
,
Thomas Helbing
1   Department for Cardiology and Angiology
,
Friedhelm Beyersdorf
2   Department for Cardiovascular Surgery
,
Manfred Olschewski
3   Department for Biometry and Statistics, University Hospital Freiburg, Freiburg, Germany
,
Christoph Bode
1   Department for Cardiology and Angiology
,
Martin Moser
1   Department for Cardiology and Angiology
› Author AffiliationsFinancial support: Work in M.M.‘s lab is supported by intramural funds and the Deutsche Forschungsgemeinschaft SFB-TR 23.
Further Information

Publication History

Received: 07 May 2007

Accepted after major revision: 06 February 2008

Publication Date:
25 November 2017 (online)

Also available at
    Permissions and Reprints

Summary

The mechanisms of the progression of aortic valve stenosis are unknown. The involvement of mononuclear cells and of chronic systemic inflammation has been suggested by analysis of pathological specimens. We hypothesize that shear stress caused by the constricted aortic orifice contributes to systemic proinflammation by activation of circulating blood cells and thereby generation of microparticles. Using flow cytometry we analyzed 22 patients with severe aortic valve stenosis (AVS) and 18 patient controls for the generation of circulating microparticles from platelet-(PMPs: CD31+/CD61+ or CD62P+), leukocyte-(LMPs: CD11b+) and endothelial cell (EMPs: CD62E+) origin. Apart from the constricted valve orifice groups were similar. PMPs were increased in AVS patients and their number correlated with valvular shear stress. Monocytes were activated in AVS patients, an observation that was also reflected by increased numbers of LMPs and by the detection of PMP-monocyte conjugates. Furthermore, EMPs reflecting the activation of endothelial cells but also conferring systemic inflammatory activity were increased in AVS patients and correlated with the number of activated monocytes. In conclusion, we show that AVS is accompanied by increased levels of microparticles and that shear stress can induce the formation of microparticles. Based on our results and histologic findings of other investigators the speculation that shear stress related to aortic valve stenosis induces a vicious circle including the generation of PMPs, the subsequent activation of monocytes and LMPs and finally the activation of endothelial cells contributing to the progress of aortic valve stenosis appears to be justified.

Keywords

Microparticles - aortic valve stenosis - endothelial activation

* These authors contributed equally.


 

  • References

  • 1 Galante A, Pietroiusti A, Vellini M. et al. C-reactive protein is increased in patients with degenerative aortic valvular stenosis. J Am Coll Cardiol 2001; 38: 1078-1082.
    CrossrefPubMedSearch in Google Scholar
  • 2 Mazzone A, Epistolato MC, Gianetti J. et al. Biological features (inflammation and neoangiogenesis) and atherosclerotic risk factors in carotid plaques and calcified aortic valve stenosis: two different sites of the same disease?. Am J Clin Pathol 2006; 126: 494-502.
    CrossrefPubMedSearch in Google Scholar
  • 3 Martinez MC, Tesse A, Zobairi F. et al. Shed membrane microparticles from circulating and vascular cells in regulating vascular function. Am J Physiol Heart Circ Physiol 2005; 288: H1004-1009.
    CrossrefPubMedSearch in Google Scholar
  • 4 Hugel B, Martinez MC, Kunzelmann C. et al. Membrane microparticles: two sides of the coin. Physiology (Bethesda) 2005; 20: 22-27.
    CrossrefPubMedSearch in Google Scholar
  • 5 Sabatier F, Roux V, Anfosso F. et al. Interaction of endothelial microparticles with monocytic cells in vitro induces tissue factor-dependent procoagulant activity. Blood 2002; 99: 3962-3970.
    CrossrefPubMedSearch in Google Scholar
  • 6 Distler JH, Pisetsky DS, Huber LC. et al. Microparticles as regulators of inflammation: novel players of cellular crosstalk in the rheumatic diseases. Arthritis Rheum 2005; 52: 3337-3348.
    CrossrefPubMedSearch in Google Scholar
  • 7 Koga H, Sugiyama S, Kugiyama K. et al. Elevated levels of remnant lipoproteins are associated with plasma platelet microparticles in patients with type-2 diabetes mellitus without obstructive coronary artery disease. Eur Heart J 2006; 27: 817-823.
    CrossrefPubMedSearch in Google Scholar
  • 8 Barry OP, Pratico D, Lawson JA. et al. Transcellular activation of platelets and endothelial cells by bioactive lipids in platelet microparticles. J Clin Invest 1997; 99: 2118-2127.
    CrossrefPubMedSearch in Google Scholar
  • 9 Daniel L, Fakhouri F, Joly D. et al. Increase of circulating neutrophil and platelet microparticles during acute vasculitis and hemodialysis. Kidney Int 2006; 69: 1416-1423.
    CrossrefPubMedSearch in Google Scholar
  • 10 Esposito K, Ciotola M, Schisano B. et al. Endothelial microparticles correlate with endothelial dysfunction in obese women. J Clin Endocrinol Metab 2006; 91: 3676-3679.
    CrossrefPubMedSearch in Google Scholar
  • 11 Mezentsev A, Merks RM, O’Riordan E. et al. Endothelial microparticles affect angiogenesis in vitro: role of oxidative stress. Am J Physiol Heart Circ Physiol 2005; 289: H1106-1114.
    CrossrefPubMedSearch in Google Scholar
  • 12 Goto S, Ikeda Y, Saldivar E. et al. Distinct mechanisms of platelet aggregation as a consequence of different shearing flow conditions. J Clin Invest 1998; 101: 479-486.
    CrossrefPubMedSearch in Google Scholar
  • 13 Boulanger CM, Scoazec A, Ebrahimian T. et al. Circulating microparticles from patients with myocardial infarction cause endothelial dysfunction. Circulation 2001; 104: 2649-2652.
    CrossrefPubMedSearch in Google Scholar
  • 14 Arteaga RB, Chirinos JA, Soriano AO. et al. Endothelial microparticles and platelet and leukocyte activation in patients with the metabolic syndrome. Am J Cardiol 2006; 98: 70-74.
    CrossrefPubMedSearch in Google Scholar
  • 15 Beckman JA, Creager MA, Libby P. Diabetes and atherosclerosis: epidemiology, pathophysiology, and management. J Am Med Assoc 2002; 287: 2570-2581.
    CrossrefPubMedSearch in Google Scholar
  • 16 van der Zee PM, Biro E, Ko Y. et al. P-selectin-and CD63-exposing platelet microparticles reflect platelet activation in peripheral arterial disease and myocardial infarction. Clin Chem 2006; 52: 657-664.
    CrossrefPubMedSearch in Google Scholar
  • 17 Morel N, Morel O, Delabranche X. et al. Microparticles during sepsis and trauma. A link between inflammation and thrombotic processes. Ann Fr Anesth Reanim 2006; 25: 955-966.
    CrossrefPubMedSearch in Google Scholar
  • 18 Ogura H, Tanaka H, Koh T. et al. Enhanced production of endothelial microparticles with increased binding to leukocytes in patients with severe systemic inflammatory response syndrome. J Trauma 2004; 56: 823-830 discussion 830-821.
    CrossrefPubMedSearch in Google Scholar
  • 19 Minagar A, Jy W, Jimenez JJ. et al. Elevated plasma endothelial microparticles in multiple sclerosis. Neurology 2001; 56: 1319-1324.
    CrossrefPubMedSearch in Google Scholar
  • 20 Amabile N, Guerin AP, Leroyer A. et al. Circulating endothelial microparticles are associated with vascular dysfunction in patients with end-stage renal failure. J Am Soc Nephrol 2005; 16: 3381-3388.
    CrossrefPubMedSearch in Google Scholar
  • 21 Kim HK, Song KS, Park YS. et al. Elevated levels of circulating platelet microparticles, VEGF, IL-6 and RANTES in patients with gastric cancer: possible role of a metastasis predictor. Eur J Cancer 2003; 39: 184-191.
    CrossrefPubMedSearch in Google Scholar
  • 22 Bonow RO, Carabello BA, Kanu C. et al. ACC/ AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing committee to revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): developed in collaboration with the Society of Cardiovascular Anesthesiologists: endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons. Circulation 2006; 114: e84-231.
    CrossrefPubMedSearch in Google Scholar
  • 23 Lang RM, Bierig M, Devereux RB. et al. Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr 2005; 18: 1440-1463.
    CrossrefPubMedSearch in Google Scholar
  • 24 Keuren JF, Magdeleyns EJ, Govers-Riemslag JW. et al. Effects of storage-induced platelet microparticles on the initiation and propagation phase of blood coagulation. Br J Haematol 2006; 134: 307-313.
    CrossrefPubMedSearch in Google Scholar
  • 25 Fujimi S, Ogura H, Tanaka H. et al. Increased production of leukocyte microparticles with enhanced expression of adhesion molecules from activated polymorphonuclear leukocytes in severely injured patients. J Trauma 2003; 54: 114-120.
    CrossrefPubMedSearch in Google Scholar
  • 26 Jy W, Horstman LL, Jimenez JJ. et al. Measuring circulating cell-derived microparticles. J Thromb Haemost 2004; 2: 1842-1843.
    CrossrefPubMedSearch in Google Scholar
  • 27 Jy W, Mao WW, Horstman L. et al. Platelet microparticles bind, activate and aggregate neutrophils in vitro. Blood Cells Mol Dis 1995; 21: 217-231 discussion 231a.
    CrossrefPubMedSearch in Google Scholar
  • 28 Chirinos JA, Heresi GA, Velasquez H. et al. Elevation of endothelial microparticles, platelets, and leukocyte activation in patients with venous thromboembolism. J Am Coll Cardiol 2005; 45: 1467-1471.
    CrossrefPubMedSearch in Google Scholar
  • 29 Ahrens IG, Moran N, Aylward K. et al. Evidence for a differential functional regulation of the two beta(3)- integrins alpha(V)beta(3) and alpha(IIb)beta(3). Exp Cell Res 2006; 312: 925-937.
    CrossrefPubMedSearch in Google Scholar
  • 30 Mesri M, Altieri DC. Endothelial cell activation by leukocyte microparticles. J Immunol 1998; 161: 4382-4387.
    PubMedSearch in Google Scholar
  • 31 Ghaisas NK, Foley JB, O’Briain DS. et al. Adhesion molecules in nonrheumatic aortic valve disease: endothelial expression, serum levels and effects of valve replacement. J Am Coll Cardiol 2000; 36: 2257-2262.
    CrossrefPubMedSearch in Google Scholar
  • 32 Pfister SL. Role of platelet microparticles in the production of thromboxane by rabbit pulmonary artery. Hypertension 2004; 43: 428-433.
    CrossrefPubMedSearch in Google Scholar
  • 33 Joop K, Berckmans RJ, Nieuwland R. et al. Microparticles from patients with multiple organ dysfunction syndrome and sepsis support coagulation through multiple mechanisms. Thromb Haemost 2001; 85: 810-820.
    Thieme ConnectPubMedSearch in Google Scholar
  • 34 Cauwenberghs S, Feijge MA, Harper AG. et al. Shedding of procoagulant microparticles from unstimulated platelets by integrin-mediated destabilization of actin cytoskeleton. FEBS Lett 2006; 580: 5313-5320.
    CrossrefPubMedSearch in Google Scholar
  • 35 Atkinson C, Zhu H, Qiao F. et al. Complement-dependent P-selectin expression and injury following ischemic stroke. J Immunol 2006; 177: 7266-7274.
    CrossrefPubMedSearch in Google Scholar
  • 36 Polgar J, Matuskova J, Wagner DD. The P-selectin, tissue factor, coagulation triad. J Thromb Haemost 2005; 3: 1590-1596.
    CrossrefPubMedSearch in Google Scholar
  • 37 Mesri M, Altieri DC. Leukocyte microparticles stimulate endothelial cell cytokine release and tissue factor induction in a JNK1 signaling pathway. J Biol Chem 1999; 274: 23111-23118.
    CrossrefPubMedSearch in Google Scholar
  • 38 Chironi G, Simon A, Hugel B. et al. Circulating leukocyte-derived microparticles predict subclinical atherosclerosis burden in asymptomatic subjects. Arterioscler Thromb Vasc Biol 2006; 26: 2775-2780.
    CrossrefPubMedSearch in Google Scholar
  • 39 Jy W, Minagar A, Jimenez JJ. et al. Endothelial microparticles (EMP) bind and activate monocytes: elevated EMP-monocyte conjugates in multiple sclerosis. Front Biosci 2004; 9: 3137-3144.
    CrossrefPubMedSearch in Google Scholar
  • 40 Brogan PA, Dillon MJ. Endothelial microparticles and the diagnosis of the vasculitides. Intern Med 2004; 43: 1115-1119.
    CrossrefPubMedSearch in Google Scholar
  • 41 Poggianti E, Venneri L, Chubuchny V. et al. Aortic valve sclerosis is associated with systemic endothelial dysfunction. J Am Coll Cardiol 2003; 41: 136-141.
    PubMedSearch in Google Scholar
  • 42 Fox CS, Guo CY, Larson MG. et al. Relations of inflammation and novel risk factors to valvular calcification. Am J Cardiol 2006; 97: 1502-1505.
    CrossrefPubMedSearch in Google Scholar
  • 43 Schonenberger A, Winkelspecht B, Kohler H. et al. High prevalence of aortic valve alterations in haemodialysis patients is associated with signs of chronic inflammation. Nephron Clin Pract 2004; 96: c48-55.
    CrossrefPubMedSearch in Google Scholar
  • 44 Klinkner DB, Densmore JC, Kaul S. et al. Endothelium-derived microparticles inhibit human cardiac valve endothelial cell function. Shock 2006; 25: 575-580.
    CrossrefPubMedSearch in Google Scholar
  • 45 Sanchez PL, Santos JL, Kaski JC. et al. Relation of circulating C-reactive protein to progression of aortic valve stenosis. Am J Cardiol 2006; 97: 90-93.
    CrossrefPubMedSearch in Google Scholar
  • 46 Sanchez PL, Mazzone A. C-reactive protein in degenerative aortic valve stenosis. Cardiovasc Ultrasound 2006; 4: 24.
    CrossrefPubMedSearch in Google Scholar