Inflammation and the Osteogenic Regulation of Vascular Calcification: A Review and Perspective

Abstract

Arterial biomineralization processes have been afflicting humans for ≥5 millennia, as realized in 2003 via the computed tomographic imaging of Otzi, the intriguing “ice mummy” discovered in the Tyrolean Alps.1 Patchy abdominal atherosclerotic calcification was readily detected in the postmortem of this ≈40-year-old hunter of the early Copper Age, by 2000 years a predecessor of King Tutankhamen.1 Today, an epidemic of vascular calcification is emerging within our aging and dysmetabolic populace.2,3 Although vascular calcification was once considered only a passive process of dead and dying cells, work from laboratories worldwide has now highlighted that arterial biomineralization is an actively regulated form of calcified tissue metabolism.4,5 Moreover, as in skeletal development – where unique biology controls matrix mineralization in membranous bone, endochondral bone, dentin, and enamel,6,7 mechanistic diversity exists in the pathobiology of vascular calcium deposition.2,4,5,8 Five common forms of vascular calcification, each possessing unique histoanatomic characteristics and clinical settings with overlapping yet distinct molecular mechanisms, have been described to date4,5,9 (Table 1⇓⇓). Although we touch on the subject, the reader is referred to other contemporary reviews for in-depth consideration of pathogenic differences.2,4,5 View this table: Table 1. Common Histoanatomic Forms of Vascular Calcification and Clinical Settings 2,4,5,11,99 View this table: Table 1. Continued View this table: Table 1. Continued In this brief review and perspective, we recount recent data that emphasize inflammation and oxidative stress signaling as key contributors to the pathogenesis of vascular mineral deposition.10 Furthermore, we highlight differences between the low-density lipoprotein receptor (LDLR)-deficient and apolipoprotein E (apoE)-deficient murine models (Table 2) that help articulate the multifaceted contributions of dyslipidemia, diabetes mellitus, and uremia to arterial calcium deposition.2,4,11 We end by summarizing the importance of considering these disease stage- and context-specific contributions arterial mineralization when crafting therapeutic strategies to address the disease burden of vascular …