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BDNFVal66met polymorphism: a potential bridge between depression and thrombosis.
- Source :
- European Heart Journal; 5/7/2017, Vol. 38 Issue 18, p1426-1435, 10p, 1 Chart, 7 Graphs
- Publication Year :
- 2017
-
Abstract
- Aims: 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. Methods and results: BDNF<superscript>Met/Met</superscript> mice displayed a depressive-like phenotype concomitantly with hypercoagulable state and platelet hyperreactivity. Proteomic analysis of aorta secretome from BDNF<superscript>Met/Met</superscript> 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 BDNF<superscript>Met</superscript> 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 BDNF<superscript>Met/Met</superscript> 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 inWT mice and cells. Finally, we found that BDNF Met homozygosity is associated with increased risk of acute myocardial infarction (AMI) in humans. Conclusion: Activation of platelets, alteration in coagulation pathways, and changes in vessel wall protein expression in BDNF<superscript>Met/Met</superscript> 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 0195668X
- Volume :
- 38
- Issue :
- 18
- Database :
- Complementary Index
- Journal :
- European Heart Journal
- Publication Type :
- Academic Journal
- Accession number :
- 123002137
- Full Text :
- https://doi.org/10.1093/eurheartj/ehv655