Patho- physiological role of BDNF in fibrin clotting

Area of Science:

• Biochemistry
• Cardiovascular Biology
• Hematology

Background:

• Circulating Brain Derived Neurotrophic Factor (BDNF) levels are reduced in coronary heart disease (CHD) patients and correlate with adverse cardiovascular events.
• The precise mechanisms linking low BDNF to increased thrombotic risk in CHD remain incompletely elucidated.

Purpose of the Study:

• To investigate the role of BDNF in modulating fibrin clot structure and stability.
• To explore the potential of BDNF as a factor influencing thrombus formation and resolution in the context of CHD.

Main Methods:

• Recombinant human BDNF (rh-BDNF) was used to assess its effects on fibrin clot formation in purified fibrinogen and plasma from healthy subjects.
• Clot properties including fibrin fiber density, maximum clot firmness (MCF), turbidity, and lysis were evaluated.
• Thrombin and reptilase clotting times were measured, alongside thrombin generation.
• Fibrin clot morphology in CHD patient plasma was analyzed before and after rh-BDNF treatment.

Main Results:

• rh-BDNF reduced fibrin fiber density, maximum clot firmness (MCF), and turbidity in a concentration-dependent manner.
• rh-BDNF affected clot lysis and prolonged thrombin and reptilase clotting times, despite increased thrombin formation.
• CHD patients exhibited lower BDNF levels, denser fibrin fibers, and higher MCF compared to controls, with an inverse correlation between BDNF and MCF.
• rh-BDNF treatment normalized fibrin clot morphology in CHD patient plasma.

Conclusions:

• Reduced circulating BDNF levels in CHD are associated with altered fibrin structure, leading to increased clot density and firmness (in vitro).
• BDNF plays a significant role in regulating fibrin fiber formation and clot stability, potentially influencing thrombus resolution.
• These findings suggest a novel mechanism linking BDNF deficiency to enhanced thrombotic risk in coronary heart disease.