Upregulation of CD40-CD40 Ligand (CD154) in Patients With Acute Cerebral Ischemia

Garlichs, Christoph D.; Kozina, S.; Fateh-Moghadam, Suzanne; Tomandl, Bernd; Stumpf, Christian; Eskafi, Saeed; Raaz, Dorette; Schmeißer, Alexander; Yılmaz, Atilla; Ludwig, Joseph A.; Neundörfer, B.; Daniel, Werner G.

doi:10.1161/01.str.0000074032.64049.47

Cited by 140 publications

(123 citation statements)

References 32 publications

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“…Circulating levels of soluble CD40 ligand (sCD40L) are upregulated in systemic vascular diseases, such as ischemic heart disease, stroke, pulmonary hypertension, and even in cigarette smokers (12,16,19,20). Furthermore, we found that CD40 stimulation induces emphysematous change in mouse lung.…”

Section: Sensitization Of Fas-mediated Cell Death By Cd40 And/or Ifn-mentioning

confidence: 85%

CD40 amplifies Fas-mediated apoptosis: a mechanism contributing to emphysema

Shigeta¹,

Tada²,

Wang

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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Section: Sensitization Of Fas-mediated Cell Death By Cd40 And/or Ifn-mentioning

confidence: 85%

CD40 amplifies Fas-mediated apoptosis: a mechanism contributing to emphysema

Shigeta¹,

Tada²,

Wang

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Recent studies demonstrated that sCD40L is enhanced in patients at risk of CVD and in those with acute coronary syndrome suggesting that it may represent a new marker of atherosclerotic progression [16][17][18][19][20]. The behaviour of sCD40L has never been explored in patients with metabolic syndrome.…”

Section: Introductionmentioning

confidence: 99%

Enhanced soluble CD40L in patients with the metabolic syndrome: relationship with in vivo thrombin generation

et al. 2006

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Aims/hypothesis: The metabolic syndrome is associated with proinflammatory and prothrombotic states. This study was designed to assess the behaviour of soluble CD40 ligand (sCD40L) and prothrombin fragment F 1+2 , a marker of thrombin generation, in patients with the metabolic syndrome. Methods: We investigated 106 patients with the metabolic syndrome, diagnosed according to the ATPIII report, and 104 subjects without the metabolic syndrome. Results: Plasma values of sCD40L and F 1+2 were higher in patients with the metabolic syndrome (4.11±1.64 vs 2.61±0.89 ng/ml and 1.54±0.49 vs 0.87±0.21 nmol/l, respectively; p<0.001) and were significantly correlated (r=0.925, p<0.001). Stepwise multiple linear regression analysis showed that sCD40L was significantly associated with F 1+2 , female sex and waist circumference.Conclusions/interpretation: Patients with the metabolic syndrome have enhanced values of plasma sCD40L and F 1+2 . The study provides further insight into the relationship between metabolic syndrome, inflammation and thrombosis.

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“…Overexpression of CD40 ligand (CD40L; CD154), a key immune and inflammatory mediator, has emerged as an important contributor to inflammation and atherosclerosis. [1][2][3][4][5][6][7][8] Clinically, elevated levels of circulating soluble CD40L (sCD40L) have been associated with hypercholesterolemia, diabetes, ischemic stroke and acute coronary syndromes, and predict increased restenosis after percutaneous coronary (and carotid) intervention (PCI). 8 -12 Whereas the role of CD40L in experimental atherosclerosis has been examined extensively, relatively little is known about the contribution of elevated CD40L to neointima formation and restenosis, particularly in an atherogenic environment.…”

mentioning

confidence: 99%

CD40 Ligand Promotes Mac-1 Expression, Leukocyte Recruitment, and Neointima Formation after Vascular Injury

Sanders

Bevard

et al. 2008

The American Journal of Pathology

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High levels of circulating soluble CD40 ligand (sCD40L) are frequently found in patients with hypercholesterolemia, diabetes, ischemic stroke, or acute coronary syndromes, predicting an increased rate of atherosclerotic plaque rupture and restenosis after coronary/carotid interventions. Clinical restenosis is characterized in part by exaggerated neointima formation, but the underlying mechanism remains incompletely understood. This study investigated the role of elevated sCD40L in neointima formation in response to vascular injury in an atherogenic animal model and explored the molecular mechanisms involved. apoE ؊/؊ mice fed a Western diet developed severe hypercholesterolemia, significant hyperglycemia, and high levels of plasma sCD40L. Neointima formation after carotid denudation injury was exaggerated in the apoE ؊/؊ mice. In vivo, blocking CD40L with anti-CD40L monoclonal antibody attenuated the early accumulation of Ly-6G؉ neutrophils and Gr-1 ؉ monocytes (at 3 days) and the late accumulation of Mac-2 ؉ macrophages (at 28 days) in the denudated arteries; it also reduced the exaggerated neointima formation at 28 days. In vitro, recombinant CD40L stimulated platelet P-selectin and neutrophil Mac-1 expression and platelet-neutrophil co-aggregation and adhesive interaction. These effects were abrogated by anti-CD40L or anti-Mac-1 monoclonal antibody. Moreover, recombinant CD40L stimulated neutrophil oxidative burst and release of matrix metalloproteinase-9 in vitro. We conclude that elevated sCD40L promotes platelet-leukocyte activation and recruitment and neointima formation after arterial injury, potentially through enhancement of platelet P-selectin and leukocyte Mac-1 expression and oxidative activity. (Am J

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Upregulation of CD40-CD40 Ligand (CD154) in Patients With Acute Cerebral Ischemia

Abstract: Patients with acute cerebral ischemia show upregulation of the CD40 system, which might contribute to the known proinflammatory, proatherogenic, and prothrombotic milieu found in these patients.

Cited by 140 publications

References 32 publications

CD40 amplifies Fas-mediated apoptosis: a mechanism contributing to emphysema

CD40 amplifies Fas-mediated apoptosis: a mechanism contributing to emphysema

Enhanced soluble CD40L in patients with the metabolic syndrome: relationship with in vivo thrombin generation

CD40 Ligand Promotes Mac-1 Expression, Leukocyte Recruitment, and Neointima Formation after Vascular Injury

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