Raised serum levels of soluble CD40 ligand in patients with familial hypercholesterolemia: downregulatory effect of statin therapy

Semb, Anne Grete; Wissen, Sanne van; Ueland, Thor; Smilde, Tineke J.; Wæhre, Torgun; Tripp, Mieke D; Frøland, Stig S.; Kastelein, John J.P.; Gullestad, Lars; Pedersen, Terje R.; Aukrust, Pål; Stalenhoef, Anton F. H.

doi:10.1016/s0735-1097(02)02718-3

Cited by 102 publications

(79 citation statements)

References 29 publications

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“…[16][17][18][19] There is evidence that the sCD40L level is a strong predictor of cardiovascular risk. 20 In literature, enhanced levels of CD40L were reported in patients with hypercholesterolemia, [21][22][23] diabetes mellitus, 24,25 and acute coronary syndromes. [26][27][28][29] Few studies have reported the relationship between obesity and sCD40L.…”

Section: Soluble Cd40 Ligand and C-reactive Proteinmentioning

confidence: 99%

The Levels of Soluble CD40 Ligand and C-Reactive Protein in Normal Weight, Overweight and Obese People

Ünek

Bayraktar²,

Solmaz³

et al. 2010

Clinical Medicine & Research

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Objective: Obesity has been suggested as an independent risk factor for cardiovascular disease. Increasing evidence shows that engagement of soluble CD40 ligand (sCD40L) with its receptor plays a crucial role in the pathogenesis of atherosclerosis. The aim of the present study was to test whether obesity is associated with low-grade systemic inflammation as measured by serum high-sensitive C-reactive protein (hsCRP) and sCD40L concentration.Methods: Serum hsCRP and sCD40L concentrations were measured in 148 nondiabetic people. The participants were divided into three groups depending upon their body mass index (BMI) levels: Group 1 (normal weight), BMI<25 kg/m 2 ; Group 2 (overweight), BMI 25 kg/m 2 to 29.9 kg/m 2 ; and Group 3 (obese), BMI≥30 kg/m 2 .Results: Obese people had more elevated hsCRP levels than both their normal weight and overweight counterparts (P=0.000 and P=0.000, respectively). Similarly, serum concentrations of sCD40L were significantly higher, statistically, in obese subjects compared with normal weight subjects (P=0.003). In addition, obese subjects had higher values of sCD40L than overweight subjects, but the difference did not reach statistical significance (P=0.063). The levels of high-density lipoprotein cholesterol were significantly lower in obese subjects compared to normal weight subjects (P=0.048). The analysis of platelet count disclosed a statistically significant difference between obese subjects and normal weight subjects (P=0.028). The levels of BMI were positively correlated with the serum levels of hsCRP and sCD40L in all subjects (r=0.514, P=0.000 and r=0.283, P=0.000, respectively). Levels of hsCRP were positively correlated with waist circumference, fasting glucose, total cholesterol, triglyceride, low-density lipoprotein cholesterol, leukocytes, platelets, systolic and diastolic blood pressure. Similarly, soluble CD40L levels were positively correlated with waist circumference, fasting glucose and leukocytes. Conclusion:Obese patients showed a significant increase of hsCRP and sCD40L levels compared with normal weight subjects, which might contribute to the known proinflammatory milieu found in these patients.

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Section: Soluble Cd40 Ligand and C-reactive Proteinmentioning

confidence: 99%

The Levels of Soluble CD40 Ligand and C-Reactive Protein in Normal Weight, Overweight and Obese People

Ünek

Bayraktar²,

Solmaz³

et al. 2010

Clinical Medicine & Research

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“…25 Statin treatment significantly reduces CD40 and CD40L expression and lowers sCD40L in patients with familial hypercholesterolemia. 70 Blockade of CD40L by neutralizing antibodies or genetic disruption of CD40L in mice appears to prevent the initiation and progression of atherosclerosis and induces a more stable plaque with fewer inflammatory cells, less lipids, and more smooth muscle cells and collagen. 71,72 Elevated levels of soluble and membranebound forms of CD40L have been reported for patients with angina, 73 after cardiopulmonary bypass surgery, 74 and with congestive heart failure.…”

Section: Cd40/cd40l Interactionsmentioning

confidence: 99%

Modulation of the Inflammatory Response in Cardiovascular Disease

2004

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Abstract-There is a growing body of evidence that inflammation might play an important role in the initiation and progression of cardiovascular diseases (CVDs). The designation of CVD as a chronic inflammatory process is further supported by evidence that the risk factors for CVD cause endothelial cells throughout the vascular tree to assume an inflammatory phenotype. These activated endothelial cells characteristically exhibit oxidative stress and increased adhesiveness for circulating leukocytes. Although initial efforts to define the mechanisms underlying the inflammatory phenotype in diseased endothelial cells have focused on the linkage between oxidative stress and adhesion molecule activation/expression, recent work has implicated a variety of additional factors that can modulate the magnitude and/or nature of the inflammatory responses in CVD. Platelets, angiotensin II, and the CD40/CD40 ligand signaling system are gaining recognition as contributors to the pathogenesis of CVD. These factors appear to converge with known pathways that link oxidative stress with adhesion molecule expression and help to explain the apparent integration of coagulation with inflammation in CVD. These factors also hold the promise of offering multiple sites for therapeutic intervention in CVD. Key Words: oxidative stress Ⅲ integrins Ⅲ angiotensin II Ⅲ adhesion molecules I nflammation is gaining widespread attention for its role in the initiation and progression of cardiovascular disease (CVD). Epidemiological studies have revealed strong associations between biochemical markers of systemic inflammation and both the presence of and future risk for symptomatic CVD. Animal experimentation as well as clinical studies has provided convincing evidence that the known risk factors for CVD (hypertension, diabetes, hypercholesterolemia, and smoking) can elicit both an inflammatory and a prothrombogenic phenotype in the vascular system. The phenotypic changes are more pronounced in endothelial cells and can include oxidative stress, increased expression of endothelial cell adhesion molecules (CAMs), activation of cell signaling pathways (eg, the CD40/CD40 ligand [CD40L] dyad), and the consequent adhesion and activation of leukocytes and platelets. In the microcirculation, the inflammatory manifestations of CVD are more readily visible in postcapillary venules. There is growing evidence, however, that the endothelium-dependent arteriolar dysfunction often associated with CVD is also linked to the systemic inflammatory response. [1][2][3][4] Because the expression of adhesion glycoproteins by activated endothelial cells is a rate-determining step in the recruitment of inflammatory cells, much attention has been devoted to the role of endothelial CAMs in CVD. This attention has produced considerable evidence for the: (1) altered endothelial CAM expression in animal models of CVD 2,5 ; (2) use of circulating levels of soluble endothelial CAMs (eg, soluble intercellular adhesion molecule-1 [sICAM-1]) as a marker for the severity of inflammati...

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“…In a study of patients with stable coronary syndromes or strong family history of cardiovascular disease, both conventional and more aggressive statin therapy decreased sCD40L over 2 years, with greater lowering at 2 years than at 1 year. 19 In addition to the fact that different patients were studied (those with stable coronary syndromes), in that study, sCD40L was measured from serum after the blood samples were allowed to clot. 19 sCD40L concentrations tend to be higher in serum (reflecting greater release from platelets activated by clot formation) than in EDTA plasma such as was used in the present study.…”

Section: Effect Of Statin Therapymentioning

confidence: 99%

“…15,18 Two studies in patients with stable coronary syndromes also indicate that statins may reduce sCD40L. 18,19 However, the impact of statins on sCD40L in patients with acute coronary syndromes has not been studied prospectively in a large randomized, controlled trial.…”

mentioning

confidence: 99%

Effect of Atorvastatin on Risk of Recurrent Cardiovascular Events After an Acute Coronary Syndrome Associated With High Soluble CD40 Ligand in the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Study

et al. 2004

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Raised serum levels of soluble CD40 ligand in patients with familial hypercholesterolemia: downregulatory effect of statin therapy

Abstract: Our findings may suggest enhanced CD40L-CD40 interaction in FH and that this inflammatory response may be downregulated by statins.

Cited by 102 publications

References 29 publications

The Levels of Soluble CD40 Ligand and C-Reactive Protein in Normal Weight, Overweight and Obese People

The Levels of Soluble CD40 Ligand and C-Reactive Protein in Normal Weight, Overweight and Obese People

Modulation of the Inflammatory Response in Cardiovascular Disease

Effect of Atorvastatin on Risk of Recurrent Cardiovascular Events After an Acute Coronary Syndrome Associated With High Soluble CD40 Ligand in the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Study

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