Kv1.3 Channel, a Targetable Piece in the Complex Jigsaw Puzzle of Vascular Calcification?

Abstract

In parallel with an unprecedented progress in vascular and stem cell biology during the past two decades, our understanding of vascular calcification has evolved from being perceived as a harmless, passive deposition of minerals to what we now consider a highly regulated, cell-mediated process that is strongly associated with chronic kidney disease (CKD) and confers increased risk for incident cardiovascular disease. A PubMed search of the term “vascular calcification” reveals an impressive exponential growth in the number of original articles published between 2000-2015, but this trend seems to have slowed down in the past 5-6 years. Studies have helped us understand that vascular calcification can engage a large number of key mediators and signalling pathways and that its anatomical and histological location can determine the type and severity of the clinical outcomes. Despite this significantly increased knowledge regarding the underlying pathophysiology, very little progress has been made when it comes to therapies and only a handful of interventional studies have documented any impact on vascular calcification other than modest effects in slowing down the process. The reasons for this lack of translational progress are many, including a somewhat conventional view of vascular calcification with most interventions aiming at restoring or reverting the uremic environment or targeting calcification too late in the process. In this issue of Function, Cazana-Perez et al provide new mechanistic insight in the regulation of vascular calcification, directing our attention to the vascular smooth muscle cell (VSMC), one of the main drivers in both medial and intimal calcification. (Less)