Preprocedural Level of Soluble CD40L Is Predictive of Enhanced Inflammatory Response and Restenosis After Coronary Angioplasty

Cipollone, Francesco; Ferri, Claudio; Desideri, Giovambattista; Paloscia, Leonardo; Materazzo, Guido; Mascellanti, Marco; Fazia, Maria; Iezzi, Annalisa; Cuccurullo, Chiara; Pini, Barbara; Bucci, Marco; Santucci, A.; Cuccurullo, Franco; Mezzetti, Andrea

doi:10.1161/01.cir.0000103700.05109.0d

Cited by 100 publications

(38 citation statements)

References 20 publications

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“…[13][14][15][16] However, it remains unclear whether and how elevated sCD40L contributes to neointima formation, a prominent feature of restenosis. There are several important findings in the present study.…”

Section: Discussionmentioning

confidence: 99%

“…Cipollone et al 13 reported that preprocedural levels of plasma sCD40L were significantly higher in patients that developed restenosis than in patients with favorable outcomes, and raised sCD40L at baseline was significantly correlated with circulating adhesion molecules (sICAM-1, sVCAM-1, sE-selectin), plasma monocyte chemoattractant protein-1 after PCI, and with lumen loss at 6-month follow-up. Turker et al 14 reported that preprocedural levels of plasma sCD40L were significantly higher and more prolonged in patients with in-stent restenosis compared with patients without in-stent restenosis at 6-month follow-up.…”

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confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

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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“…The isolation and culture of peripheral monocytes from five healthy blood donors and the analysis of O 2 − generation was assessed as previously described [9,14]. Synthetic sCD40L (10 ng/ml and 1-10 μg/ml), anti-human blocking monoclonal antibody for CD40L (10 μg/ml) (Alexis), or control mouse IgG 1 (50 μg/ml) were added to some cell cultures.…”

Section: Scd40l-dependent Monocyte Activationmentioning

confidence: 99%

“…Recently the presence of T cells expressing CD40L within atherosclerotic lesions in humans has been reported [3], and the ability of gene disruption or anti-CD40L antibody treatment to limit the evolution and the instability of atherosclerotic plaque has been described [4]. Increased soluble CD40L (sCD40L) has been observed in unstable angina [5] and hypercholesterolaemia [6], and it has been recently reported that circulating sCD40L has a strong independent prognostic value among apparently healthy individuals [7] and patients with acute coronary syndromes [8,9].…”

Section: Introductionmentioning

confidence: 99%

Enhanced soluble CD40 ligand contributes to endothelial cell dysfunction in vitro and monocyte activation in patients with diabetes mellitus: effect of improved metabolic control

et al. 2005

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Aims/hypothesis: Inflammation plays a pathogenic role in the development of accelerated atherosclerosis in diabetes. Soluble CD40 ligand (sCD40L) is enhanced in diabetes; however, the molecular mechanisms linking sCD40L to accelerated atherosclerosis in diabetes are still unclear. We tested the hypothesis that sCD40L may be involved in the vascular complications in diabetes and exerts its effect by triggering inflammatory reactions on mononuclear and endothelial cells (ECs). Methods: We studied 70 patients, 40 with type 2 and 30 with type 1 diabetes, with a history or physical examination negative for cardiovascular disease, and 40 non-diabetic and 30 healthy subjects, matched with the type 2 and type 1 diabetic patients, respectively. Plasma and serum sCD40L, and plasma soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, E-selectin and monocyte chemo-attractant protein-1 (MCP-1) were measured. Adhesion molecules and MCP-1 release, the ability to repair an injury in ECs, and O 2 − generation in monocytes were analysed in vitro after stimulation with serum from patients or controls. Results: Type 2 and type 1 diabetic patients had significantly higher sCD40L levels than controls. Furthermore, high sCD40L was associated with in vitro adhesion molecules and MCP-1 release, impaired migration in ECs and enhanced O 2 − generation in monocytes. Improved metabolic control was associated with a reduction of plasma sCD40L by 37.5% in 12 type 1 diabetic patients. Furthermore, elevated sCD40L in diabetic patients was significantly correlated with HbA 1 c levels. Conclusions/interpretation: Upregulation of sCD40L as a consequence of persistent hyperglycaemia in diabetic patients results in EC activation and monocyte recruitment to the arterial wall, possibly contributing to accelerated atherosclerosis development in diabetes.

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“…Studies found that elevated sCD40L in acute coronary syndrome is associated with increased risk of death or recurrent infarction (10,16). In addition, Mezzetti et al (17) reported that the preprocedural level of sCD40L is predictive of enhanced immune response and restenosis after angioplasty.…”

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confidence: 99%

Coronary artery disease progression is associated with C-reactive protein and conventional risk factors but not soluble CD40 ligand

Liang

Sheu

Lee

et al. 2006

Canadian Journal of Cardiology

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BACKGROUND: Coronary artery disease (CAD) is a major cause of death worldwide. Epidemiological studies have documented conventional risk factors; however, no studies to date have addressed the roles of soluble CD40 ligand (sCD40L) and monocyte chemoattractant protein-1 (MCP-1), and there have been few reports on other novel risk factors in CAD progression. The aim of the present study was to explore the roles of novel and conventional risk factors in CAD progression. METHODS: Patients with stable angina pectoris who underwent repeat coronary angiograms and had serum samples at the time of their first catheterizaton between March 1999 and January 2004 were enrolled. Those who had progression of coronary atherosclerosis were classified into the progression group (n=66). Those who did not have CAD progression were classified into the nonprogression group (n=124). RESULTS: There were more cases of diabetes mellitus (36% versus 20%; P=0.024) and more men (92% versus 81%; P=0.040) in the CAD progression group than in the nonprogression group, respectively. The progression group also had poorer lipid profiles than the nonprogression group, including higher total cholesterol (188±42 mg/dL versus 173±39 mg/dL, respectively; P=0.014) and low density lipoprotein cholesterol (122±38 mg/dL versus 112±36 mg/dL, respectively; P=0.025). In terms of inflammatory markers, progression patients had higher baseline high-senstivity C-reactive protein (hs-CRP) concentrations (P=0.018), which was also related to the subsequent angiographic severity score changes; however, sCD40L (6182±4352 pg/mL versus 6244±4602 pg/mL; P=0.961), MCP-1 (427±540 pg/mL versus 341±128 pg/mL; P=0.580) and adhesion molecules concentrations were indifferent between the progression group and the nonprogression group, respectively. Using a multivariate logistical regression model, the ORs for predicting progression were 2.19 for diabetes mellitus, 2.04 for hypercholesterolemia and 1.52 for hs-CRP (P<0.05). CONCLUSION: In the present study, only conventional risk factors, and particularly hs-CRP, were markers for predicting CAD progression. Novel risk factors, such as concentrations of sCD40L, MCP-1 and adhesion molecules, did not play significant roles.

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Preprocedural Level of Soluble CD40L Is Predictive of Enhanced Inflammatory Response and Restenosis After Coronary Angioplasty

Cited by 100 publications

References 20 publications

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

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

Enhanced soluble CD40 ligand contributes to endothelial cell dysfunction in vitro and monocyte activation in patients with diabetes mellitus: effect of improved metabolic control

Coronary artery disease progression is associated with C-reactive protein and conventional risk factors but not soluble CD40 ligand

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