PDF herunterladen
Thromb Haemost 2012; 107(02): 346-355
DOI: 10.1160/TH11-05-0345
Cardiovascular Biology and Cell Signalling
Schattauer GmbH

Upregulation of CD40 ligand and enhanced monocyte-platelet aggregate formation are associated with worse clinical outcome after ischaemic stroke

Maria Lukasik
1   Department of Neurology, Poznan University of Medical Sciences, Poznan, Poland
,
Grzegorz Dworacki
2   Department of Clinical Immunology, Poznan University of Medical Sciences, Poznan, Poland
,
Joanna Kufel-Grabowska
1   Department of Neurology, Poznan University of Medical Sciences, Poznan, Poland
,
Cezary Watala
3   Department of Haemostatic Disorders, Medical University of Lodz, Lodz, Poland
,
Wojciech Kozubski
1   Department of Neurology, Poznan University of Medical Sciences, Poznan, Poland
› Institutsangaben
Financial support: This study was supported financially by the governmental research grant NN 402366233.
Weitere Informationen

Publikationsverlauf

Received: 23. Mai 2011

Accepted after major revision: 01. Januar 2011

Publikationsdatum:
29. November 2017 (online)

Auch verfügbar auf
   Lizenzen und Reprints

Summary

The white blood cell count and mean platelet volume determined shortly after the symptom onset are known as independent predictors for clinical outcome after stroke. In the present study we sought to evaluate the prognostic value of platelet-derived inflammatory biomarkers measured prospectively after an ischaemic event. Using five-colour flow cytometry, the platelet surface expression of CD40L, CD62P and subpopulations of leukocyte-platelet aggregates were assessed in 93 stroke patients on the first (V0), 10th (V1) and 90th (V2) day after stroke, and once in 65 disease controls. The clinical outcome was evaluated using the Scandinavian Stroke Scale (SSS) and modified Rankin Scale (mRS) at the same time points as blood sampling and 24 months after the event. Patients with either CD40L surface expression or the percentage of monocyte-platelet aggregates (M-plt) in the third tertile (T3) at V0 had a significantly lower score on the SSS at V1. Patients with the percentage M-plt at V0 higher than the median value of M-plt in controls were at increased risk of SSS < 40 at V1 (odds ratio: 2.6; 95% confidence interval [CI]: 1.4 – 8.7; p=0.006). Patients with the percentage of M-plt in T3 at V0 showed progressive decline in survival (hazard ratio [HR]: 1.6; 95% CI: 1.1–1.9; p=0.02) and a significantly higher number of recurrent vascular events (HR: 2.64; 95% CI: 1.3–3.2; p=0.02) when compared to the first tertile. In conclusion, increased levels of M-plt could be a predictive marker for both early outcome and long-term prognosis while increased CD40L was correlated with worse clinical outcome.

The preliminary results of this study were presented in part during a poster session at the 62nd Annual Meeting of the American Academy of Neurology in Toronto, 7–17 April 2010.

Keywords

Leukocyte-platelet aggregates - CD40L - stroke - prognostic factors
 

  • References

  • 1 Kazmierski R, Guzik P, Ambrosius W. et al. Predictive value of white blood cell count on admission for in-hospital mortality in acute stroke patients.. Clin Neurol Neurosurg 2004; 107: 38-43.
    CrossrefPubMedSuche in Google Scholar
  • 2 Elkind MSV, Cheng J, Rundek T. et al. Leukocyte count predicts outcome after ischemic stroke: the Northern Manhattan Stroke Study.. J Stroke Cerebrovasc Dis 2004; 13: 220-227.
    CrossrefPubMedSuche in Google Scholar
  • 3 Grau AJ, Boddy AW, Dukovic DA. et al. for the CAPRIE Investigators. Leukocyte count as an independent predictor of recurrent ischemic events. Stroke 2004; 35: 1147-1152.
    CrossrefPubMedSuche in Google Scholar
  • 4 Bath P, Algert C, Chapman N. et al. PROGRESS Collaborative Group. Associations of mean platelet volume with risk of stroke among 3134 individuals with history of cerebrovascular disease. Stroke 2004; 35: 622-626.
    CrossrefPubMedSuche in Google Scholar
  • 5 Michelson AD, Barnard MR, Hechtman H. et al. In vivo tracking of platelets: circulating degranulated platelets rapidly lose surface P-selectin but continue to circulate and function. Proc Natl Acad Sci USA 1996; 93: 11877-11883.
    CrossrefPubMedSuche in Google Scholar
  • 6 Anand SX, Viles-Gonzalez JF, Badimon JJ. et al. Membrane-associated CD40L and sCD40L in atherothrombotic disease.. Thromb Haemost 2003; 90: 377-384.
    Thieme ConnectPubMedSuche in Google Scholar
  • 7 Michelson AD, Barnard MR, Krueger LA. et al. Circulating monocyte-platelet aggregates are a more sensitive marker of in vivo platelet activation than platelet surface P-selectin: studies in baboons, human coronary intervention, and human acute myocardial infarction.. Circulation 2001; 104: 1533-1537.
    CrossrefPubMedSuche in Google Scholar
  • 8 Adams Jr HP, Bendixen BH, Kappelle LJ. et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke 1993; 24: 35-41.
    CrossrefPubMedSuche in Google Scholar
  • 9 Bamford J, Sandercock P, Dennis M. et al. Classification and natural history of clinically identifiable subtypes of cerebral infarction. Lancet 1991; 337: 1521-1526.
    CrossrefPubMedSuche in Google Scholar
  • 10 Sacco RL.. Risk factors and outcomes for ischemic stroke. Neurology 1995; 45: S4-10.
    CrossrefPubMedSuche in Google Scholar
  • 11 Garlichs CD, Kozina S, Fateh-Moghadam S. et al. Upregulation of CD40-CD40 ligand (CD154) in patients with acute cerebral ischemia.. Stroke 2003; 34: 1412-1418.
    CrossrefPubMedSuche in Google Scholar
  • 12 McCabe DJH, Harrison P, Mackie IJ. et al. Platelet degranulation and monocyte-platelet complex formation are increased in the acute and convalescent phases after ischaemic stroke or transient ischaemic attack.. Br J Haematol 2004; 125: 777-787.
    CrossrefPubMedSuche in Google Scholar
  • 13 Glass CK, Witztum JL.. Atherosclerosis: the road ahead. Cell 2001; 104: 503-516.
    CrossrefPubMedSuche in Google Scholar
  • 14 Yilmaz G, Granger DN.. Leukocyte recruitment and ischemic brain injury. Neuromol Med 2010; 12: 193-204.
    CrossrefPubMedSuche in Google Scholar
  • 15 Barone FC, Hillegass LM, Tzimas MN. et al. Time-related changes in myeloperoxidase activity and leukotriene B4 receptor binding reflect leukocyte influx in cerebral focal stroke. Mol Chem Neuropathol 1995; 24: 13-30.
    CrossrefPubMedSuche in Google Scholar
  • 16 Weyrich AS, Elstad MR, McEver RP. et al. Activated platelets signal chemokine synthesis by human monocytes. J Clin Invest 1996; 97: 1525-1534.
    CrossrefPubMedSuche in Google Scholar
  • 17 Fitzgerald GA.. COX-2 and beyond: approaches to prostaglandin inhibition in human disease. Nat Rev Dug Discov 2003; 2: 879-890.
    PubMedSuche in Google Scholar
  • 18 Galt SW, Lindemann S, Medd D. et al. Differential regulation of matrix metalloproteinase-9 by monocytes adherent to collagen and platelets.. Circ Res 2008; 102: 302-309.
    CrossrefPubMedSuche in Google Scholar
  • 19 Schonbeck U, Libby P.. CD40 signaling and plaque instability. Circ Res 2001; 89: 1092-1103.
    CrossrefPubMedSuche in Google Scholar
  • 20 von Hundelshausen P, Weber KS, Huo Y. et al. RANTES deposition by platelets triggers monocyte arrest on inflamed and atherosclerotic endothelium.. Circulation 2001; 103: 1772-1777.
    CrossrefPubMedSuche in Google Scholar
  • 21 Dixon DA, Tolley ND, Bemis-Standoli K. et al. Expression of COX-2 in platelet-monocyte interactions occurs via combinatorial regulation involving adhesion and cytokine signaling.. J Clin Invest 2006; 95: 2297-2303.
    PubMedSuche in Google Scholar
  • 22 Welsh P, Lowe GD, Chalmers J. et al. Associations of proinflammatory cytokines with the risk of recurrent stroke.. Stroke 2008; 39: 2226-2230.
    CrossrefPubMedSuche in Google Scholar
  • 23 Ishikawa M, Cooper D, Russel J. et al. Molecular determinants of the prothrombogenic and inflammatory phenotype assumed by the postischemic cerebral microcirculation.. Stroke 2003; 34: 1777-1782.
    CrossrefPubMedSuche in Google Scholar
  • 24 Li G, Sanders JM, Bevard MH. et al. CD40 ligand promotes Mac-1 expression, leukocyte recruitment, and neointima formation after vascular injury. Am J Pathol 2008; 172: 1141-1152.
    CrossrefPubMedSuche in Google Scholar
  • 25 Garlichs CD, Johm S, Schmeisser Y. et al. Upregulation of CD40-CD40 ligand (CD154) in patients with moderate hypercholesterolemia. Circulation 2001; 104: 2395-2400.
    CrossrefPubMedSuche in Google Scholar
  • 26 Cipollone F, Ferri C, Desideri G. et al. Preprocedural level of soluble CD40L is predictive of enhanced inflammatory response and restenosis after coronary angioplasty. Circulation 2003; 108: 2776-2782.
    CrossrefPubMedSuche in Google Scholar
  • 27 Michelson AD, Barnard MR, Krueger LA. et al. Circulating monocyte-platelet aggregates are a more sensitive marker of in vivo platelet activation than platelet surface P-selectin: studies in baboons, human coronary intervention, and human acute myocardial infarction.. Circulation 2001; 104: 1533-1537.
    CrossrefPubMedSuche in Google Scholar
  • 28 Aslanyan S, Weir CJ, Diener HC. et al. GAIN International Steering Committee and Investigators. Pneumonia and urinary tract infection after acute ischemic stroke: a tertiary analysis of the GAIN International Trial. Eur J Neurol 2004; 11: 49-53.
    CrossrefPubMedSuche in Google Scholar
  • 29 Urra X, Cervera A, Obach V. et al. Monocytes are major players in the prognosis and risk of infection after acute stroke.. Stroke 2009; 40: 1262-1268.
    CrossrefPubMedSuche in Google Scholar
  • 30 Urra X, Villamor N, Amaro S. et al. Monocyte subtypes predict clinical course and prognosis in human stroke.. J Cerebr Blood Flow Metab 2009; 29: 994-1002.
    PubMedSuche in Google Scholar
  • 31 Vargas M, Horcajada JP, Obach V. et al. Clinical consequences of infection in patients with acute stroke: is it prime time for further antibiotic trials?. Stroke 2006; 37: 461-465.
    CrossrefPubMedSuche in Google Scholar