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December 26, 2021Biomedicine & PharmacotherapyOpen Access

The α2-adrenergic receptor pathway modulating depression influences the risk of arterial thrombosis associated with BDNFVal66Met polymorphism

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Key result

The BDNF Met allele dysregulates the norepinephrine/α2A-ADR pathway, leading to platelet hyper-reactivity and increased procoagulant activity in CAD patients and mice.

Why the study?

Depression is associated with thrombotic risk, and the depression-related BDNFVal66Met polymorphism has been linked to arterial thrombosis in mice and acute myocardial infarction in humans.

Does modulation of the norepinephrine/α2A-ADR pathway reduce arterial thrombosis risk in BDNFMet/Met models?

Population

Homozygous knock-in BDNFMet/Met mice, in vitro cell models, and CAD patients with BDNFMet/Met or BDNFVal/Val

Comparison

Desipramine, rauwolscine, or BDNFMet/Met genotype vs controls or BDNFVal/Val

Design

Preclinical in vivo, in vitro, and translational human observational study

Authors

LSLeonardo SandriniPAPatrizia AmadioAIAlessandro Ieraci

Discussion

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Member takes

Overview

May warrant caution selecting antidepressants in depressed CAD patients; leaves open genotype-specific thrombotic effects.

Structured PICO

Does modulation of the norepinephrine/α2A-ADR pathway reduce arterial thrombosis risk in BDNFMet/Met models?

P
Population
Homozygous knock-in BDNF Val66Met (BDNFMet/Met) mice, in vitro cell models, and coronary artery disease (CAD) patients with homozygous BDNFMet/Met or BDNFVal/Val genotypes
E
Exposure
Desipramine (norepinephrine reuptake-inhibitor) or rauwolscine (α2-ADR antagonist)
C
Comparator
Untreated/control models or BDNFVal/Val patients
O
Outcome
Arterial thrombosis risk, platelet reactivity, and procoagulant activitysurrogate

The BDNF Met allele dysregulates the norepinephrine/α2A-ADR pathway, predisposing to arterial thrombosis, suggesting that α2A-ADR inhibitors could be a targeted treatment for depression-associated thrombotic conditions in specific CAD patients.

Cite This Study

Sandrini et al. (2021) studied Coronary artery disease. BDNFVal66Met polymorphism vs. BDNFVal/Val was evaluated on Platelet hyper-reactivity and procoagulant activity. The BDNF Met allele dysregulates the norepinephrine/α2A-ADR pathway, leading to platelet hyper-reactivity and increased procoagulant activity in CAD patients and mice.

synapsesocial.com/papers/6a6ba74f26cff2e2f6f474a0https://doi.org/10.1016/j.biopha.2021.112557
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Reduced thrombus stability in mice lacking the α2A-adrenergic receptor2006 · 67 citations
  2. 2Depression and coronary heart disease: 2018 position paper of the ESC working group on coronary pathophysiology and microcirculation2019 · 401 citations
  3. 3Abnormal megakaryopoiesis and platelet function in cyclooxygenase-2-deficient mice2015 · 16 citations
  4. 4The Associations between Central Nervous System Diseases and Haemostatic Disorders2019 · 2 citations
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