BackgroundIt is becoming increasingly evident that platelet chemokines are involved in distinct aspects of atherosclerosis. The aim of this study was to examine the effects of long-term supplementation with purified anthocyanins on platelet chemokines in hypercholesterolemic individuals and to identify correlations of decreased platelet chemokine levels with serum lipid and inflammatory marker levels.MethodsA total of 146 hypercholesterolemic individuals were recruited and treated with 320 mg of purified anthocyanins (n = 73) or a placebo (n = 73) daily for 24 weeks in this randomized, double-blind, placebo-controlled trial.ResultsAnthocyanin supplementation for 24 weeks significantly decreased the plasma CXCL7 (–12.32% vs. 4.22%, P = 0.001), CXCL5 (–9.95% vs. 1.93%, P = 0.011), CXCL8 (–6.07% vs. 0.66%, P = 0.004), CXCL12 (–8.11% vs. 5.43%, P = 0.023) and CCL2 levels (–11.63% vs. 12.84%, P = 0.001) compared with the placebo. Interestingly, the decreases in the CXCL7 and CCL2 levels were both positively correlated with the decreases in the serum low-density lipoprotein-cholesterol (LDL-C), high-sensitivity C-reactive protein (hsCRP) and interleukin-1β (IL-1β) levels after anthocyanin supplementation for 24 weeks. The decrease in the CXCL8 level was negatively correlated with the increase in the how-density lipoprotein-cholesterol (HDL-C) level and was positively correlated with the decrease in the soluble P-selectin (sP-selectin) level in the anthocyanin group. In addition, a positive correlation was observed between the decreases in the CXCL12 and tumornecrosis factor-α (TNF-α) levels after anthocyanin supplementation. However, the plasma CXCL4L1, CXCL1, macrophage migration inhibitory factor (MIF) and human plasminogen activator inhibitor 1 (PAI-1) levels did not significantly change following anthocyanin supplementation.ConclusionsThe present study supports the notion that platelet chemokines are promising targets of anthocyanins in the prevention of atherosclerosis.Trial registration ChiCTR-TRC-08000240. Registered: 10 December 2008.

Scope Platelet integrin αIIbβ3 is the key mediator of atherothrombosis. Supplementation of coenzyme Q10 (CoQ10), a fat‐soluble molecule that exists in various foods, exerts protective cardiovascular effects. This study aims to investigate whether and how CoQ10 acts on αIIbβ3 signaling and thrombosis, the major cause of cardiovascular diseases. Methods and results Using a series of platelet functional assays in vitro, it is demonstrated that CoQ10 reduces human platelet aggregation, granule secretion, platelet spreading, and clot retraction. It is further demonstrated that CoQ10 inhibits platelet integrin αIIbβ3 outside‐in signaling. These inhibitory effects are mainly mediated by upregulating cAMP/PKA pathway, where CoQ10 stimulates the A2A adenosine receptor and decreases phosphodiesterase 3A phosphorylation. Moreover, CoQ10 attenuates murine thrombus growth and vessel occlusion in a ferric chloride (FeCl3)‐induced thrombosis model in vivo. Importantly, the randomized, double‐blind, placebo‐controlled clinical trial in dyslipidemic patients demonstrates that 24 weeks of CoQ10 supplementation increases platelet CoQ10 concentrations, enhances the cAMP/PKA pathway, and attenuates αIIbβ3 outside‐in signaling, leading to decreased platelet aggregation and granule release. Conclusion Through upregulating the platelet cAMP/PKA pathway, and attenuating αIIbβ3 signaling and thrombus growth, CoQ10 supplementation may play an important protective role in patients with risks of cardiovascular diseases.

This study investigated whether the anthocyanin cyanidin-3-O-β-glucoside (Cy-3-g) could affect platelet apoptosis and proplatelet formation in vitro. Thrombin-stimulated or resting human platelets and Meg-01 megakaryocytes were incubated with Cy-3-g (0, 0.5, 5, or 50 μM). We found that the percentage of the platelet mitochondrial membrane potential treated with 5 and 50 μM Cy-3-g was significantly higher than control (15.50% ± 3.24% and 29.77% ± 4.06% versus 2.76% ± 1.33%, respectively; P < 0.05). Treatment with 5 and 50 μM Cy-3-g significantly increased phosphatidylserine exposure compared with control (40.56% ± 10.53% and 76.62% ± 8.28% versus 15.43% ± 3.93%, respectively; P < 0.05). Moreover, Cy-3-g significantly increased the expression of Bax, Bak, and cytochrome c while markedly decreasing Bcl-xL and Bcl-2 expression as well as stimulating caspase-3, caspase-9, caspase-8, Bid, and gelsolin cleavage in thrombin-activated platelets in a dose-dependent manner ( P < 0.05). However, no significant differences were observed in the apoptosis of resting platelets when treated with Cy-3-g ( P > 0.05). Furthermore, Cy-3-g significantly ( P < 0.05) enhanced cell viability (50 μM versus control, 1.34 ± 0.01 versus 0.35 ± 0.02), the number of colony-forming unit-megakaryocytes (50 μM versus control, 38 ± 3 versus 8 ± 3), CD41 expression (50 μM versus control, 96.80% ± 2.55% versus 25.57% ± 2.86%), DNA ploidy (16N) (50 μM versus control, 19.73% ± 2.34% versus 4.42% ± 1.96%), and proplatelet formation (50 μM versus control, 27.5% ± 3.77% versus 7.67% ± 2.25%) in Meg-01 cells. In conclusion, Cy-3-g promotes activated platelet apoptosis and enhances megakaryocyte proliferation, differentiation, and proplatelet formation in vitro.

Summary Platelet granule release is considered an important target for preventing and treating cardiovascular diseases (CVDs). Cyanidin-3-glucoside (Cy-3-g) is a predominant bioactive anthocyanin compound in many edible plants and has been reported to be protective against CVDs by attenuating platelet dysfunction. However, direct evidence of the action of Cy-3-g on platelet granule secretion in purified platelets from in vivo assays is still poor. In the present study, we demonstrated that dietary supplementation of purified Cy-3-g reduces serum lipid levels and facilitates down-regulation of the platelet granule release of substances such as P-selectin, CD40L, 5-HT, RANTES and TGF-b1 in gel-filtered platelets, in addition to attenuating serum PF4 and b-TG levels in mice fed high-fat diets. These results provide evidence that Cy-3-g protects against thrombosis and CVDs by inhibiting purified platelet granule release in vivo.