Bidirectional Translation in Cardiovascular Calcification.

Over the past decade, we have witnessed an explosion of fundamental research aimed at understanding mechanisms contributing to cardiovascular calcification. As highlighted in recent reviews, numerous animal models and patient group studies have lent key insights into mechanisms and processes underlying pathological remodeling of soft tissues, including activation of signaling cascades related to bone morphogenetic proteins, Wnt/β-catenin, matrix γ-carboxyglutamate (Gla) protein (MGP), transforming growth factor (TGF)-β, phosphate signaling, and various downstream targets. Although there are compelling data supporting the biological importance of these pathways, harnessing these mechanisms for the development of therapeutics has not yet been realized. Many pathways play an integral role in bone homeostasis, making systemic targeting a nonviable therapeutic approach. In this Recent Highlights focused on cardiovascular calcification, we have drawn from the pool of recent publications in ATVB and other leading journals that focus on genetic and nongenetic upstream modulators of ectopic calcification pathways, and we posit that interventions aimed at reducing their impact may be more readily translated to clinical therapies for patients. A greater understanding of the key local and systemic cofactors, initiators, and outcomes will create a complementary approach to advancing both science and medicine. We further argue that identification of biomarkers that are prognostic not only for the presence of vascular calcification (VC) but also for the rate of progression of VC will be instrumental in the early identification and appropriate management of patients in the future.