Diagnostic and Treatment Strategies for Cardiovascular Calcification

Joshua Hutcheson, PhD
Assistant Professor
Biomedical Engineering
Florida International University

Abstract:  Bone-like mineralization compromises the biomechanical function of diseased cardiovascular tissues. Calcification of the aortic valve and arterial walls contributes to cardiac overload and heart failure and is especially prevalent in patients with chronic kidney disease (CKD). Detectable calcification in CKD patients reduces 5-year survivability in CKD patients from approximately 90% to 50%. There are currently no effective pharmacotherapies to prevent or treat vascular calcification. Development of a therapeutic that reduces calcium mineral in the vascular wall could lower cardiovascular morbidity. The diversity of initiators complicates the development of therapies that may be broadly applicable to different patient populations. An appropriate strategy to overcome this problem may be to directly target the processes of mineral deposition. We are investigating the earliest mechanisms associated with mineral formation. The initial nucleation events begin in nano-sized extracellular vesicles (EVs) that aggregate calcium and phosphate ions. We trace these EVs to caveolae domains in the cell membrane and seek to disrupt trafficking of these domains through the cell using clinically approved small molecules. We demonstrate therapeutic efficacy of this approach in CKD models. Translating this therapeutic strategy to human patients will require the development of new diagnostic modalities that can identify patients in earlier, treatable stages of disease. Current modalities to identify the presence of calcification require complex and expensive imaging technologies that are unlikely to be performed on asymptomatic patients. Initial symptoms such as shortness of breath and fatigue are also less likely to be reported in underserved and underrepresented populations, leading to significant disparities in disease management and outcomes. In recognition of this problem, we are developing low-cost diagnostic strategies that dovetail with our therapeutic research. The combination of these point-of-care diagnostic strategies and non-invasive therapeutics could lead to significant improvement in the management of cardiovascular calcification.

Bio:  Dr. Joshua Hutcheson joined the Department of Biomedical Engineering at Florida International University (FIU) as an Assistant Professor following completion of his PhD at Vanderbilt University and postdoctoral training at Brigham and Women's Hospital/Harvard Medical School. He is also a member of the FIU Biomolecular Sciences Institute and holds a secondary appointment in the Department of Human and Molecular Genetics at the FIU Herbert Wertheim College of Medicine. His work focuses on the mechanisms through which tissues are built and maintained and the pathological changes that lead to disease. Research in Dr. Hutcheson’s lab primarily focuses on cardiovascular disease--the leading cause of death in Western societies—and combines advanced imaging, materials science, biomechanics, and molecular biology to connect cellular processes to tissue function. The overarching goal of the work is to develop new ways to detect initiators of disease and find interventions that restore diseased cardiovascular tissue to a normal state. Accomplishing these goals requires an interdisciplinary effort with researchers working at the interface between bioengineering and molecular biology. Dr. Hutcheson’s research has been supported by funding from the American Heart Association, the National Science Foundation, the Florida Heart Research Foundation, and the National Institutes of Health. In recognition of his efforts, Dr. Hutcheson was named the “Stop Heart Disease Researcher of the Year” by the Florida Heart Research Foundation in 2018.