Soluble CD40 Ligand, Soluble P-Selectin, Interleukin-6, and Tissue Factor in Diabetes Mellitus

Abstract

Background-High levels of the soluble fragment of CD40 ligand (sCD40L) have previously been associated with adverse cardiovascular outcomes. CD40L-CD40 interaction has been linked to the pathogenesis of atherothrombotic complications in cardiovascular disease (CVD). We sought to determine whether a "package of care" of intensified multifactorial cardiovascular risk intervention could reduce indices of platelet activation, inflammation, and coagulation in diabetes and whether patients with overt CVD would derive similar benefit compared with those without. Methods and Results-We measured plasma sCD40L, soluble P-selectin (sP-sel, an index of platelet activation), interleukin-6 (IL-6, a proinflammatory cytokine), and tissue factor (TF, an initiator of coagulation) in 97 patients with diabetes mellitus (41 with and 56 without overt CVD) and 39 comparable healthy control subjects. Thirty-six patients with and 32 without overt CVD then participated in a package of care of cardiovascular risk intervention over a period of 1 year. Plasma levels of sCD40L (PϽ0.001), sP-sel (PϽ0.001), IL-6 (Pϭ0.001), and TF (PϽ0.001) were higher in patients with diabetes than in control subjects, with TF levels highest in patients with overt CVD. Multifactorial intervention was associated with significant reductions in sCD40L in both patient groups (both PϽ0.001), but reductions in sP-sel and TF were seen only in patients without overt CVD. There was no significant change in IL-6 levels in both patient groups. Conclusions-Intensive multifactorial risk management can reduce high levels of sCD40L but can only partially correct abnormal platelet activation, inflammation, and coagulation in diabetes, particularly in patients with overt CVD.

Beyond Hyperglycemia in Diabetes: Role of Statin Treatment on Thrombogenesis Triggered by Inflammation

“…They show an increase of the soluble form of CD40 ligand (sCD40L) in patients with T2D, confirming previously published observations in both type 1 and 2 diabetes [15][16][17].…”

Histamine differentially interacts with tumor necrosis factor‐α and thrombin in endothelial tissue factor induction: the role of c‐Jun NH2‐terminal kinase

“…TF is known to be involved in the pathogenesis of vascular disease [12,30], and elevated levels of TF have been observed in patients with hypertension, dyslipidemia, diabetic vasculopathy, and peripheral artery disease [12,[31][32][33][34]. A pathogenetic role of histamine in atherogenesis was highlighted by recent studies demonstrating that histidine decarboxylase as well as the H 1 -receptor are expressed in atherosclerotic human arteries [11], and that mice deficient in histidine decarboxylase exhibit reduced intimal thickening after vascular injury [10].…”

The inflammatory receptor CD40 is expressed on human adipocytes: contribution to crosstalk between lymphocytes and adipocytes

“…Considerable evidence implicates the proinflammatory CD40 molecule, TNF receptor superfamily member 5 (CD40) ligand (CD40L or CD154) in atherosclerosis [2][3][4], and some recent data identify CD40/CD40L as a potential contributor to inflammation associated with obesity and its metabolic complications. Soluble CD40L (sCD40L) levels are increased in obese [5,6] and type 2 diabetic [7][8][9] individuals, as well as in individuals with the metabolic (insulin resistance) syndrome [10]. Variations in sCD40L plasma levels are strongly linked to differences in waist to hip ratio and to insulin sensitivity [11], with levels increased by exposure to hyperglycaemia and hyperinsulinaemia [12].…”