Abstract Number: PB0012
Meeting: ISTH 2020 Congress
Background: Brain-derived neurotrophic factor (BDNF) is a member of neurotrophin family, known for its role in homeostasis of cardiovascular system. Low circulating BDNF levels were associated with future coronary events, mortality and adverse left ventricular cardiac remodeling. Recently the BDNFVal66Met polymorphism was related to increased propensity for arterial thrombosis related to acute myocardial infarction.
Aims: This study investigated the effect of BDNFVal66Met polymorphism on cardiac remodeling after myocardial infarction in mice focusing on macrophage role. To sustain the relevance of data obtained in mice, the phenotype of macrophages derived from BDNFVal/Val or mutant BDNFMet/Met human patients was analyzed.
Methods: Wild-type (BDNFVal/Val) and homozygous BDNFVal66Met mice (BDNFMet/Met) underwent left anterior descending (LAD) coronary artery ligation, left ventricular parameters were obtained by cardiac magnetic resonance imaging (cMRI) and infarct size assessed by histology. Cardiac or peritoneal macrophages were isolated after LAD and thioglycollate elicitation. Human macrophages were obtained by differentiating circulating monocytes isoalted from BDNFVal/Val and BDNFMet/Met coronary heart disease patients (13/group). Mouse and human macrophages were charcatherized in terms of M1 and M2 markers by flow cytometry, qRT-PCR, and migration ability by agarose spot assay. The study complies Helsinki declaration and was approved by Centro Cardiologico Monzino Ethical Committee. All partecipants provided written informed consent.
Results: After LAD-ligation BDNFMet/Met mice displayed lower ejection fraction, higher infarct size and greater contralateral cardiomyocyte dimensions than BDNFVal/Val. Cardiac BDNFMet/Met macrophages showed an enhanced polarization towards M1 phenotype. Similarly, mutant peritoneal macrophages showed a greater expression of M1 markers, associated whit a higher round-to-spindle ratio. In addition, BDNFMet/Met macrophages exhibited increased migratory ability and expression of inflammatory genes (IL-6, TNF-α and COX-2). Human BDNFMet/Met macrophages displayed a similar phenotype to the one observed in mutant mice.
Conclusions: Overall these data suggest that BDNFVal66Met polymorphism, influencing macrophage polarization and activation, can contribute to affect cardiac remodeling after myocardial infarction.
To cite this abstract in AMA style:Sandrini L, Castiglioni L, Amadio P, Werba JP, Eligini S, Fiorelli S, Zarà M, Castiglioni S, Bellosta S, Lee FS, Sironi L, Tremoli E, Barbieri SS. BDNFVal66Met Polymorphism Affects Cardiac Remodeling and Modulates Macrophage Polarization After Myocardial Infarction [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/bdnfval66met-polymorphism-affects-cardiac-remodeling-and-modulates-macrophage-polarization-after-myocardial-infarction/. Accessed May 18, 2021.
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