stilbenes and Carotid-Artery-Thrombosis

Epidemiological studies strongly suggest a link between stress, depression, and cardiovascular diseases (CVDs); the mechanistic correlation, however, is poorly understood. A single-nucleotide polymorphism in the BDNF gene (BDNFVal66Met), associated with depression and anxiety, has been proposed as a genetic risk factor for CVD. Using a knock-in mouse carrying the BDNFVal66Met human polymorphism, which phenocopies psychiatric-related symptoms found in humans, we investigated the impact of this SNP on thrombosis.. BDNFMet/Met mice displayed a depressive-like phenotype concomitantly with hypercoagulable state and platelet hyperreactivity. Proteomic analysis of aorta secretome from BDNFMet/Met and wild-type (WT) mice showed differential expression of proteins involved in the coagulation and inflammatory cascades. The BDNF Met allele predisposed to carotid artery thrombosis FeCl3-induced and to death after collagen/epinephrine injection. Interestingly, transfection with BDNFMet construct induced a prothrombotic/proinflammatory phenotype in WT cells. SIRT1 activation, using resveratrol and/or CAY10591, prevented thrombus formation and restored the physiological levels of coagulation and of platelet markers in BDNFMet/Met mice and/or cells transfected with the Met allele. Conversely, inhibition of SIRT1 by sirtinol and/or by specific siRNA induced the prothrombotic/proinflammatory phenotype in WT mice and cells. Finally, we found that BDNF Met homozygosity is associated with increased risk of acute myocardial infarction (AMI) in humans.. Activation of platelets, alteration in coagulation pathways, and changes in vessel wall protein expression in BDNFMet/Met mice recapitulate well the features occurring in the anxiety/depression condition. Furthermore, our data suggest that the BDNFVal66Met polymorphism contribute to the individual propensity for arterial thrombosis related to AMI.

Topics: Animals; Anxiety Disorders; Aorta; Blood Coagulation; Brain-Derived Neurotrophic Factor; Carotid Arteries; Carotid Artery Thrombosis; Depressive Disorder; Disease Models, Animal; Female; Heterozygote; Homozygote; Humans; Male; Mice, Transgenic; Middle Aged; Myocardial Ischemia; Nerve Tissue Proteins; Platelet Activation; Platelet Aggregation Inhibitors; Polymorphism, Single Nucleotide; Receptors, Cell Surface; Resveratrol; Signal Transduction; Sirtuin 1; Stilbenes; Thrombosis

Resveratrol is one of the major polyphenolics in red wine that has been shown to exert the preventive effects against cardiovascular diseases. The effect of trans-resveratrol (t-RES) administered as an ingredient of the diet on the atherothrombotic tendency was assessed in genetically hypercholesterolemic mice after laser-induced damage on endothelium. Mice lacking both apolipoprotein E and low-density lipoprotein receptor (apoE-/-/LDLR-/-) were fed with a high-fat diet with or without t-RES (9.6 and 96 mg/kg diet) for 8 weeks. The atherosclerotic tendency was morphometrically analyzed in their aortae. The thrombotic tendency was determined by inducing thrombus by the irradiation of a helium-neon laser on carotid arteries of these mice with injection of Evans blue. Atherosclerotic area and thrombus size were evaluated by image analyzing in a computer system. Even though the plasma concentrations of lipids (total cholesterol and triacylglycerol) did not change in the control and t-RES groups, a significant decrease (approximately 30%) in the formation of atheroma was observed in the aortae of the t-RES group. The size of laser-induced thrombus that mostly consisted of platelet aggregates was significantly reduced (approximately 25%) in the t-RES group compared with that in the control group. Thus, t-RES orally administrated with a high-fat diet in apoE-/-/LDLR-/- mice significantly suppressed atherosclerosis in their aortae and reduced the laser-induced thrombosis in their carotid arteries.

Topics: Animals; Aortic Diseases; Apolipoproteins E; Arteriosclerosis; Carotid Artery Thrombosis; Cholesterol; Diet, Atherogenic; Dietary Fats; Drug Evaluation, Preclinical; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Platelet Aggregation; Radiation Injuries, Experimental; Receptors, LDL; Resveratrol; Stilbenes; Thrombophilia; Triglycerides

To study the effect of 3,4',5-trihydroxystibene-3-beta-mono-D-glucoside (Polydatin, Pol) on rabbit arterial thrombosis.. Rabbit arterial thrombosis was induced by vascular endothelial damage with trypsin.. It was showed that the moist weights of the thrombus were 6.6 +/- 1.8 and 4.8 +/- 1.6 mg in Pol 5 and 10 mg.kg-1 groups, respectively, which was lighter than that in control (10.9 +/- 1.9 mg, P < 0.05, P < 0.01); the platelet aggregation was inhibited simultaneously. In vitro, Pol 0.30-1.15 mmol.L-1 reduced TXA2 produced in platelets. It did not affect the production of PGI2 in cultured human umbilical vein endothelial cells.. Thrombosis was abated by Pol. The selective inhibition of production of TXA2 rather than PGI2, is one of the mechanisms involved.

Topics: Animals; Carotid Artery Thrombosis; Endothelium, Vascular; Female; Glucosides; Male; Platelet Aggregation; Platelet Aggregation Inhibitors; Rabbits; Stilbenes; Thromboxane B2