Impact of BDNF Val66Met Polymorphism on Myocardial Infarction: Exploring the Macrophage Phenotype
Autor: | José Pablo Werba, Francis S. Lee, Leonardo Sandrini, Susanna Fiorelli, Luigi Sironi, Elena Tremoli, Stefano Bellosta, Silvia Castiglioni, Sonia Eligini, Marta Zarà, Patrizia Amadio, Silvia S. Barbieri, Laura Castiglioni |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
medicine.medical_specialty medicine.medical_treatment macrophage phenotype Single-nucleotide polymorphism 030204 cardiovascular system & hematology 03 medical and health sciences 0302 clinical medicine Cardiac magnetic resonance imaging Neurotrophic factors cardiovascular disease Internal medicine Medicine Macrophage Myocardial infarction lcsh:QH301-705.5 BDNF Val66Met polymorphism biology medicine.diagnostic_test business.industry Growth factor General Medicine medicine.disease Thrombosis 030104 developmental biology Endocrinology myocardial infarction nervous system lcsh:Biology (General) biology.protein business Neurotrophin |
Zdroj: | Cells, Vol 9, Iss 1084, p 1084 (2020) Cells Volume 9 Issue 5 |
ISSN: | 2073-4409 |
Popis: | Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin growth factor family, well known for its role in the homeostasis of the cardiovascular system. Recently, the human BDNF Val66Met single nucleotide polymorphism has been associated with the increased propensity for arterial thrombosis related to acute myocardial infarction (AMI). Using cardiac magnetic resonance imaging and immunohistochemistry analyses, we showed that homozygous mice carrying the human BDNF Val66Met polymorphism (BDNFMet/Met) undergoing left anterior descending (LAD) coronary artery ligation display an adverse cardiac remodeling compared to wild-type (BDNFVal/Val). Interestingly, we observed a persistent presence of pro-inflammatory M1-like macrophages and a reduced accumulation of reparative-like phenotype macrophages (M2-like) in the infarcted heart of mutant mice. Further qPCR analyses showed that BDNFMet/Met peritoneal macrophages are more pro-inflammatory and have a higher migratory ability compared to BDNFVal/Val ones. Finally, macrophages differentiated from circulating monocytes isolated from BDNFMet/Met patients with coronary heart disease displayed the same pro-inflammatory characteristics of the murine ones. In conclusion, the BDNF Val66Met polymorphism predisposes to adverse cardiac remodeling after myocardial infarction in a mouse model and affects macrophage phenotype in both humans and mice. These results provide a new cellular mechanism by which this human BDNF genetic variant could influence cardiovascular disease. |
Databáze: | OpenAIRE |
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