2020 Jeffrey M. Hoeg Award Lecture: Calcifying Extracellular Vesicles as Building Blocks of Microcalcifications in Cardiovascular Disorders

Cardiovascular calcification is an insidious form of ectopic tissue mineralization that presents as a frequent comorbidity of atherosclerosis, aortic valve stenosis, diabetes, renal failure, and chronic inflammation. Calcification of the vasculature and heart valves contributes to mortality in these diseases. An inability to clinically image or detect early microcalcification coupled with an utter lack of pharmaceutical therapies capable of inhibiting or regressing entrenched and detectable macrocalcification has led to a prominent and deadly gap in care for a growing portion of our rapidly aging population. Recognition of this mounting concern has arisen over the past decade and led to a series of revolutionary works that has begun to pull back the curtain on the pathogenesis, mechanistic basis, and causative drivers of cardiovascular calcification. Central to this progress is the discovery that calcifying extracellular vesicles act as active precursors of cardiovascular microcalcification in diverse vascular beds. More recently, the omics revolution has resulted in the collection and quantification of vast amounts of molecular-level data. As the field has become poised to leverage these resources for drug discovery, new means of deriving relevant biological insights from these rich and complex datasets have come into focus through the careful application of systems biology and network medicine approaches. As we look onward toward the next decade, we envision a growing need to standardize approaches to study this complex and multifaceted clinical problem and expect that a push to translate mechanistic findings into therapeutics will begin to finally provide relief for those impacted by this disease.