Anti-CD40 monoclonal antibody, clone 6D4 [APC]

Coenzyme Q10 (CoQ10) exists in a wide variety of foods and has promising cardiovascular benefits. However, its effects on platelets and integrin alpha IIb beta 3 signaling during atherosclerosis have not been previously explored. Here, apolipoprotein E-deficient (ApoE(-/-)) mice were fed a standard diet, high-fat diet (HFD) or CoQ10-supplemented HFD for 12 weeks. We found that CoQ10 supplementation in ApoE(-/-) mice significantly alleviated formation of HFD-induced atherosclerotic lesions, and attenuated platelet hyper-aggregation and granule secretion, including CD62P, CD63 and CD40 ligand (CD40L) expression and platelet factor-4, beta-thromboglobulin and activation normal T cell expressed and secreted (CCL5) release. CoQ10 supplementation decreased soluble fibrinogen and JON/A binding to alpha IIb beta 3 on activated platelets, indicating that alpha IIb beta 3-mediated inside-out signaling was attenuated. Additionally, CoQ10 down-regulated platelet alpha IIb beta 3 outside-in signaling including decreasing phosphorylation of the beta 3 intracellular tail, cellular and sarcoma tyrosine-protein kinase (c-Src), and myosin light chain (MLC), and consistently attenuating platelet spreading and clot retraction. Importantly, platelet-monocyte aggregation that was primarily mediated by alpha IIb beta 3 and can be blocked using an alpha IIb beta 3-specific antagonist tirofiban was also markedly diminished by CoQ10. Thus, CoQ10 supplementation attenuates platelet hyper-reactivity via down-regulating both alpha IIb beta 3 inside-out and outside-in signaling, which may play important preventive roles in atherothrombosis.

OBJECTIVES: Both off-pump coronary artery bypass grafting surgery (OPCABG) and mini-extracorporeal circulation (MECC) have been associated with lower morbidity and mortality and less inflammation than conventional cardiopulmonary bypass. However, studies comparing the 2 techniques are scarce and the results are controversial. We compared the clinical outcomes and inflammatory response of low-risk patients undergoing coronary bypass grafting with MECC versus OPCABG. METHODS: We conducted a prospective, randomized study in patients undergoing coronary heart surgery. Two hundred and thirty consecutive low-risk patients were randomly assigned to either receive OPCABG (n=117) or MECC (n=113). Clinical outcomes and postoperative biochemical results were analysed in both groups. We also analysed 19 circulating inflammatory markers in a subgroup of 40 patients at 4 perioperative time points. The area under the curve for each marker was calculated to monitor differences in the inflammatory response. RESULTS: No significant differences were found between groups regarding perioperative clinical complications and no deaths occurred during the trial. Plasma levels in 9 of the 19 inflammatory markers were undetectable or showed no temporal variation, 3 were higher in the MECC group [interleukin (IL)-10, macrophage inflammatory protein-1 beta and epidermal growth factor] and 7 were higher in the OPCABG group (growth regulator oncogene, IL-6, IL-8, soluble CD40 ligand, monocyte chemoattractant protein-1, monocyte chemoattractant protein-3 and tumour necrosis factor-alpha). Differences in 2 proinflammatory cytokines, IL-6 and monocyte chemoattractant protein 1, between the 2 surgical procedures were statistically significant. CONCLUSIONS: No clinical differences were observed between in low-risk patients undergoing MECC or OPCABG surgery, but OPCABG was associated with an increased release of proinflammatory cytokines compared with MECC. Studies in larger cohorts and in patients at higher risk are needed to confirm these findings.