Impact of BDNF Val66Met Polymorphism on Myocardial Infarction: Exploring the Macrophage Phenotype

被引：18

作者：

Sandrini, Leonardo ^{[1
]}

Castiglioni, Laura ^{[2
]}

Amadio, Patrizia ^{[1
]}

Werba, Jose Pablo ^{[1
]}

Eligini, Sonia ^{[1
]}

Fiorelli, Susanna ^{[1
]}

Zara, Marta ^{[1
]}

Castiglioni, Silvia ^{[3
]}

Bellosta, Stefano ^{[3
]}

Lee, Francis S. ^{[4
]}

Sironi, Luigi ^{[1
,2
]}

Tremoli, Elena ^{[1
]}

Barbieri, Silvia Stella ^{[1
]}

机构：

[1] Ctr Cardiol Monzino IRCCS, I-20138 Milan, Italy

[2] Univ Milan, Dipartimento Sci Farmaceut, I-20133 Milan, Italy

[3] Univ Milan, Dipartimento Sci Farmacol & Biomol, I-20133 Milan, Italy

[4] Weill Cornell Med Coll, Dept Psychiat, New York, NY 10065 USA

来源：

CELLS | 2020年 / 9卷 / 05期

关键词：

BDNF Val66Met polymorphism; myocardial infarction; macrophage phenotype; cardiovascular disease; NEUROTROPHIC FACTOR; ENDOTHELIAL-CELLS; CIGARETTE-SMOKE; STEADY-STATE; MONOCYTES; POLARIZATION; TRAFFICKING; MECHANISMS; SURVIVAL; DELETION;

D O I：

10.3390/cells9051084

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页数：14

共 48 条

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