Plant Food Delphinidin-3-Glucoside Significantly Inhibits Platelet Activation and Thrombosis: Novel Protective Roles against Cardiovascular Diseases

Delphinidin-3-glucoside (Dp-3-g) is one of the predominant bioactive compounds of anthocyanins in many plant foods. Although several anthocyanin compounds have been reported to be protective against cardiovascular diseases (CVDs), the direct effect of anthocyanins on platelets, the key players in atherothrombosis, has not been studied. The roles of Dp-3-g in platelet function are completely unknown. The present study investigated the effects of Dp-3-g on platelet activation and several thrombosis models in vitro and in vivo. We found that Dp-3-g significantly inhibited human and murine platelet aggregation in both platelet-rich plasma and purified platelets. It also markedly reduced thrombus growth in human and murine blood in perfusion chambers at both low and high shear rates. Using intravital microscopy, we observed that Dp-3-g decreased platelet deposition, destabilized thrombi, and prolonged the time required for vessel occlusion. Dp-3-g also significantly inhibited thrombus growth in a carotid artery thrombosis model. To elucidate the mechanisms, we examined platelet activation markers via flow cytometry and found that Dp-3-g significantly inhibited the expression of P-selectin, CD63, CD40L, which reflect platelet α- and δ-granule release, and cytosol protein secretion, respectively. We further demonstrated that Dp-3-g downregulated the expression of active integrin αIIbβ3 on platelets, and attenuated fibrinogen binding to platelets following agonist treatment, without interfering with the direct interaction between fibrinogen and integrin αIIbβ3. We found that Dp-3-g reduced phosphorylation of adenosine monophosphate-activated protein kinase, which may contribute to the observed inhibitory effects on platelet activation. Thus, Dp-3-g significantly inhibits platelet activation and attenuates thrombus growth at both arterial and venous shear stresses, which likely contributes to its protective roles against thrombosis and CVDs

Flavanols and Anthocyanins in Cardiovascular Health: A Review of Current Evidence

Nowadays it is accepted that natural flavonoids present in fruits and plant-derived-foods are relevant, not only for technological reasons and organoleptic properties, but also because of their potential health-promoting effects, as suggested by the available experimental and epidemiological evidence. The beneficial biological effects of these food bioactives may be driven by two of their characteristic properties: their affinity for proteins and their antioxidant activity. Over the last 15 years, numerous publications have demonstrated that besides their in vitro antioxidant capacity, certain phenolic compounds, such as anthocyanins, catechins, proanthocyanidins, and other non coloured flavonoids, may regulate different signaling pathways involved in cell survival, growth and differentiation. In this review we will update the knowledge on the cardiovascular effects of anthocyanins, catechins and proanthocyanidins, as implied by the in vitro and clinical studies on these compounds. We also review the available information on the structure, distribution and bioavailability of flavanols (monomeric catechins and proanthocyanidins) and anthocyanins, data necessary in order to understand their role in reducing risk factors and preventing cardiovascular health problems through different aspects of their bioefficacy on vascular parameters (platelet agregation, atherosclerosis, blood pressure, antioxidant status, inflammation-related markers, etc.), myocardial conditions, and whole-body metabolism (serum biochemistry, lipid profile), highlighting the need for better-designed clinical studies to improve the current knowledge on the potential health benefits of these flavonoids to cardiovascular and metabolic health

914-68 SDZ GPI 562, an Oral Peptidomimetic Inhibitor of the Platelet GpIIbIIIaAbolishes Epinephrine and Shear Induced Cyclic Flow Reductions in Stenosed Monkey Carotid Arteries

Aspirin (ASA) is the only oral agent approved as an anti platelet agent (AA) to prevent platelet mediated thrombosis (PMT) myocardial infarction, strokes and reocclusion after thrombolysis or angioplasty. However, animal and human platelets inhibited with ASA can be reactivated to produce PMT with elevated plasma epinephrine levels or increased shear stress. In 7 anesthetized monkeys (M), mechanical carotid artery stenosis (MCAS) 70% diameter reduction with intimal damage was produced and blood flow measured (EMF probe). Cyclic flow reductions (CFR's) occurred due to acute PMT followed by embolization to the brain, ASA, 5mg/kg IV, abolished the CFR's in all M but they returned with Epinephrine (E), 0,2μ/kg given IV, or increase in MCAS to 85%, due to shear induced aggregation. In 8 M with 70% MCAS, after 30 minutes of CFR's, 1–2mg/kg of the drug SDZ GPl562 was given by stomach tube. Eighty-five±22 min after SDZ GPI 562, the CFR's were abolished in all 8M. Template bleeding time increased from a control of 2.3±1.0 min to 4.1±1.2 min (p<0.05) Ex vivo whole blood platelet aggregation (collagen stimulus) decreased by 76±8% (p<0,0001) and by 83±10% (p<0.0001) to ADP after SDZ GPI 562, The CFR's due to periodic acute PMT were not renewed by E, 0.2 μ/kg/min given IV for 20 minutes and/or by increased stenosis from 70% to 85% diameter reduction which increases shear from 144±15 Pa to 266±22 Pa (p<0.005). CFR's due to acute PMT have been observed in patient coronary arteries at the time of angioplasty inspire of pretreatment with aspirin and heparin but could be abolished with c7E3, a monoclonal antibody inhibitor of the platelet Gpllbilia which is available only for IV use. SDZ GPI 562 is likely to be a superior AA because it is available in oral or IV form, it blocks the final step in platelet activation by blocking the platelet GpIIbIIIa, thus protecting against platelet activation by elevated E and shear stress produced by very severe stenosis. It is also likely to be more effective than ASA for reducing the platelet contribution to atherosclerosis preventing coronary thrombosis and fatal or non fatal myocardial infarction and early and late PMT after angioplasty or atherectomy procedures