PMID- 30347685
OWN - NLM
STAT- MEDLINE
DCOM- 20190121
LR  - 20190121
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 19
IP  - 10
DP  - 2018 Oct 19
TI  - Sub-Chronic Stress Exacerbates the Pro-Thrombotic Phenotype in BDNF(Val/Met) 
      Mice: Gene-Environment Interaction in the Modulation of Arterial Thrombosis.
LID - 10.3390/ijms19103235 [doi]
LID - 3235
AB  - Brain-Derived Neurotrophic Factor (BDNF) Val66Met polymorphism has been 
      associated with increased susceptibility to develop mood disorders and recently 
      it has been also linked with cardiovascular disease (CVD). Interestingly, 
      stressful conditions unveil the anxious/depressive-like behavioral phenotype in 
      heterozygous BDNFVal66Met (BDNF(Val/Met)) mice, suggesting an important 
      relationship in terms of gene-environment interaction (GxE). However, the 
      interplay between stress and BDNF(Val/Met) in relation to CVD is completely 
      unknown. Here, we showed that BDNF(Val/Met) mice display a greater propensity to 
      arterial thrombosis than wild type BDNF(Val/Val) mice after 7 days of restraint 
      stress (RS). RS markedly increased the number of leukocytes and platelets, and 
      induced hyper-responsive platelets as showed by increased circulating 
      platelet/leukocyte aggregates and enhanced expression of P-selectin and GPIIbIIIa 
      in heterozygous mutant mice. In addition, stressed BDNF(Val/Met) mice had a 
      greater number of large and reticulated platelets but comparable number and 
      maturation profile of bone marrow megakaryocytes compared to BDNF(Val/Val) mice. 
      Interestingly, RS led to a significant reduction of BDNF expression accompanied 
      by an increased activity of tissue factor in the aorta of both BDNF(Val/Val) and 
      BDNF(Val/Met) mice. In conclusion, we provide evidence that sub-chronic stress 
      unveils prothrombotic phenotype in heterozygous BDNF Val66Met mice affecting both 
      the number and functionality of blood circulating cells, and the expression of 
      key thrombotic molecules in aorta. Human studies will be crucial to understand 
      whether this GxE interaction need to be taken into account in risk stratification 
      of coronary artery disease (CAD) patients.
FAU - Sandrini, Leonardo
AU  - Sandrini L
AUID- ORCID: 0000-0001-9878-8016
AD  - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di 
      Milano, 20133 Milan, Italy. leonardo.sandrini@unimi.it.
AD  - Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy. 
      leonardo.sandrini@unimi.it.
FAU - Ieraci, Alessandro
AU  - Ieraci A
AUID- ORCID: 0000-0001-6737-7695
AD  - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di 
      Milano, 20133 Milan, Italy. alessandro.ieraci@unimi.it.
FAU - Amadio, Patrizia
AU  - Amadio P
AUID- ORCID: 0000-0002-7439-2778
AD  - Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy. patrizia.amadio@ccfm.it.
FAU - Veglia, Fabrizio
AU  - Veglia F
AD  - Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy. fabrizio.veglia@ccfm.it.
FAU - Popoli, Maurizio
AU  - Popoli M
AD  - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di 
      Milano, 20133 Milan, Italy. maurizio.popoli@unimi.it.
FAU - Lee, Francis S
AU  - Lee FS
AD  - Department of Psychiatry, Weill Cornell Medical College of Cornell University, 
      New York, NY 10065, USA. fslee@med.cornell.edu.
FAU - Tremoli, Elena
AU  - Tremoli E
AD  - Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy. elena.tremoli@ccfm.it.
FAU - Barbieri, Silvia Stella
AU  - Barbieri SS
AUID- ORCID: 0000-0002-7486-2637
AD  - Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy. silvia.barbieri@ccfm.it.
LA  - eng
GR  - number BIO33-2014: 2607452; BIO35-2015: 2617756; BIO37-2016: 2613074; BIO37-2017: 
      2631213; MPP1.2A-2018: 2634597/Italian Ministry of Health (Ricerca Corrente)/
GR  - "5 x 1000" tax (2013 and 2014)/Italian Ministry of Health/
PT  - Journal Article
DEP - 20181019
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Brain-Derived Neurotrophic Factor)
SB  - IM
MH  - Animals
MH  - Aorta/metabolism/pathology
MH  - Bone Marrow Cells/cytology
MH  - Brain-Derived Neurotrophic Factor/*genetics
MH  - Coronary Thrombosis/etiology/*genetics/pathology
MH  - *Gene-Environment Interaction
MH  - Male
MH  - Mice
MH  - Mutation, Missense
MH  - Platelet Aggregation
MH  - Stress, Psychological/*complications
PMC - PMC6214083
OTO - NOTNLM
OT  - BDNF Val66Met
OT  - sub-chronic stress
OT  - thrombosis
COIS- The authors declare no conflict of interest.
EDAT- 2018/10/24 06:00
MHDA- 2019/01/22 06:00
PMCR- 2018/10/01
CRDT- 2018/10/24 06:00
PHST- 2018/09/14 00:00 [received]
PHST- 2018/10/15 00:00 [revised]
PHST- 2018/10/17 00:00 [accepted]
PHST- 2018/10/24 06:00 [entrez]
PHST- 2018/10/24 06:00 [pubmed]
PHST- 2019/01/22 06:00 [medline]
PHST- 2018/10/01 00:00 [pmc-release]
AID - ijms19103235 [pii]
AID - ijms-19-03235 [pii]
AID - 10.3390/ijms19103235 [doi]
PST - epublish
SO  - Int J Mol Sci. 2018 Oct 19;19(10):3235. doi: 10.3390/ijms19103235.