Identification of Treatments for Hemophilic Joint Disease Through Evaluation of Vascular Defects via Optimization of Imaging Techniques

Overview

Hemophilia A (FVIII deficiency) is characterized by spontaneous bleeding in weight-bearing joints, resulting in hemophilic arthropathy (HA). Bleeding causes inflammation and hypoxia, inducing angiogenesis. Despite advances in treatment, HA still develops. The project goal was to identify treatment and treatment targets for hemophilia that prevent vascular abnormalities. The goal was approached by gaining insight into abnormal blood vessel formation through developing a 3D visualization of joint vessels, optimizing a cryomethod for immunofluorescent analysis of hard joint tissue (allowing for detection of angiogenic markers expressed in FVIII KO models), and testing the efficacy of the most promising anti-angiogenic treatment candidate targeting Vascular Endothelial Growth Factor (VEGF). It was determined that anti-VEGF significantly reduced aSMA positive vessels at week 2, abnormal blood vessels are specific to hemophilia as compared to other joint diseases, new vessel formation and vascular remodeling was increased in FVIII KO mice after bleeding but not to the same extent in WT mice subjected to joint bleeding, and lack of hemostasis drives excessive vascular changes. Furthermore, a microCT based 3D model was developed for the visualization of blood vessels and immunofluorescent staining was optimized to allow for the identification of angiogenic targets in mouse hemophilic joints after bleeding.

Competition history

JSHS 2020 Category not listed

Resources

National JSHS abstract book

Related projects

ISEF · 2019