Bibliographic Details
| Title: |
Impact of BDNF Val66Met Polymorphism on Myocardial Infarction: Exploring the Macrophage Phenotype |
| Authors: |
Leonardo Sandrini, Laura Castiglioni, Patrizia Amadio, José Pablo Werba, Sonia Eligini, Susanna Fiorelli, Marta Zarà, Silvia Castiglioni, Stefano Bellosta, Francis S. Lee, Luigi Sironi, Elena Tremoli, Silvia Stella Barbieri |
| Source: |
Cells, Vol 9, Iss 5, p 1084 (2020) |
| Publisher Information: |
MDPI AG, 2020. |
| Publication Year: |
2020 |
| Collection: |
LCC:Cytology |
| Subject Terms: |
BDNF Val66Met polymorphism, myocardial infarction, macrophage phenotype, cardiovascular disease, Cytology, QH573-671 |
| More Details: |
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. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2073-4409 |
| Relation: |
https://www.mdpi.com/2073-4409/9/5/1084; https://doaj.org/toc/2073-4409 |
| DOI: |
10.3390/cells9051084 |
| Access URL: |
https://doaj.org/article/f006bf80bcb348c686c753c35016f3be |
| Accession Number: |
edsdoj.f006bf80bcb348c686c753c35016f3be |
| Database: |
Directory of Open Access Journals |
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