Vascular Diseases in Kidney Failure
Close to 20 million Americans, or 10% of US population, suffer from the chronic kidney disease (CKD). Among a plethora of cardiovascular manifestations, CKD patients are particularly at a high risk for both venous and arterial thrombosis, especially after vascular injury (endovascular injury such as angioplasty or stents; and surgical injury such as arteriovenous fistula creation). This area of CKD management warrants urgent investigation due to the lack of risk predictors and CKD-specific therapeutic targets.
Renal failure results in the retention of several chemical compounds, which unleash cellular toxicity and hence called uremic solutes/toxins. While investigating the molecular pathogenesis of uremic toxicity, our laboratory was the first to demonstrate the prothrombotic propensity of indolic uremic solutes which inhibit the ubiquitination of tissue factor, a bona fide member of the extrinsic coagulation pathway. Further investigation revealed Aryl Hydrocarbon Receptor (AHR) pathway as a critical mediator of tissue factor ubiquitination and thrombosis. Leveraging the ligand and the mediator, our lab aims to gain a deeper understanding of the mechanism of this unique uremic thrombosis axis (uremic solutes- AHR- TF- thrombosis). In addition, we yearn to develop biomarkers and novel compounds to improve the management of the CKD patients with thrombosis after interventions in various vascular beds including coronary artery and arteriovenous fistula, etc.
Thrombosis, being a dynamic and multicomponent process, our laboratory has taken a holistic approach, under the co-directorship of Drs. Chitalia and Ravid, the Department of Medicine of BUSM, and established a Thrombosis and Hemostasis ARC which is a multidisciplinary platform of cell and molecular biologists, clinicians (cardiologists, vascular medicine, nephrologists and hematologists), computational biologists, biomedical engineers and statisticians and mathematicians to investigate various facets of thrombosis. http://www.bumc.bu.edu/evanscenteribr/the-arcs/the-arcs/