P. Amadio
EMERGING ROLE OF NEUROTROPHINS IN CARDIOVASCULAR REGULATION:IMPACT AND CHARACTERIZATION OF GENETIC VARIANT BDNF (VAL66MET) POLYMORPHISM ON THROMBOTIC EVENTS [Tesi di dottorato]
Università degli Studi di Milano, 2014-01-16

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays a key role in neuron plasticity (Donovan, et al., 2000), and vascular development (Kermani, et al., 2007). A single nucleotide polymorphism in the BDNF gene (BDNF Val66Met) has been associated with depression (Ventriglia, et al., 2002) (Momose, et al., 2002) (Sen, et al., 2003) (Neves-Pereira, et al., 2002), and recently, it has also been proposed as genetic risk factor for cardiovascular disease (CVD) (Bozzini, et al., 2009) (Jiang, et al., 2009). Intriguingly, reduced BDNF levels are detected in both depressed patients and in subjects with BDNF Val66Met polymorphism, and seem associated with increased coronary events and mortality in patients affected by acute coronary syndrome (Bozzini, et al., 2009). In this study we have assessed the impact of BDNF Val66Met polymorphism on the levels or activity of haemostatic system in relation to experimentally induced thrombosis. Humanized Val66Met BDNF homozygote knock-in mice (BDNF Met/Met) have an alterated arterial and venous thrombosis compared to BDNF Val/Val control mice. Thromboelastometry analyses showed that BDNF Met/Met mice present a significant modification both in clot firmness, clot elasticity, and in the clot formation time compared to BDNF Val/Val mice, suggesting alteration in platelet reactivity and fibrinogen, but normal levels of coagulation factors. Importantly, Tissue Factor (TF), the key activator of blood coagulation, was modified in BDNF Met/Met mice. In addition, data obtained by proteomic analysis of the aorta secretome isolated from Val/Val and Met/Met mice, confirmed with different techniques, revealed several differentially expressed proteins involved in the regulation of coagulation and thrombosis in plasma and/or aorta tissue of BDNF Met/Met compared to control mice. Our results further confirmed the emerging role of neurotrophins in cardiovascular regulation.

diritti: info:eu-repo/semantics/openAccess
In relazione con info:eu-repo/semantics/altIdentifier/hdl/2434/229417
TREMOLI, ELENA
tutor: E. Tremoli ; co-tutor: S.S. Barbieri ; coordinatore: A. Panerai
PANERAI, ALBERTO EMILIO
Settore BIO/14 - - Farmacologia


Tesi di dottorato. | Lingua: Inglese. | Paese: | BID: TD18001323