Nanoscale Architecture in Atherosclerotic Calcification

Abstract

Calcium mineral deposits are radiographically evident in the majority of significant atherosclerotic lesions.1 These deposits generally consist of a nonhomogeneous composite containing hydroxyapatite mineral nanocrystals embedded in an organic matrix including type I collagen nanofibers. The morphometry varies over a spectrum. Amorphous deposits lack organization at the light-microscopic scale, whereas bone-like deposits have varying degrees of architectural macro-organization similar to those of developing and mature skeletal bone, which also consist of a nonhomogeneous composite containing hydroxyapatite nanocrystals embedded in a collagenous organic matrix. Based on histopathologic features, the organized, bone-like deposits appear to arise from angiogenic invasion of the amorphous deposits.2 This is consistent with the known sequence of events that leads to bone formation in fracture repair, embryonic intramembranous ossification, and in embryonic endochondral ossification, where bone arises from a cartilage scaffold. See accompanying article on page 2030 The similarities between atherosclerotic calcification and osteogenesis are more than skin deep. Several investigative groups have demonstrated osteogenic features at the cellular and molecular levels, including dynamic osteogenic gene expression in vitro and in vivo as reviewed recently by Towler and colleagues.3 In this issue of ATVB , Duer and colleagues4 take this comparison to the next level—nanoscale architecture. Using solid-state nuclear magnetic resonance (NMR) techniques, they examined the mineral-organic interface in calcium deposits from atherosclerotic plaque and skeletal bone and found marked similarities. The NMR method (rotational echo double resonance) has the capacity to isolate the nanoscale features because it generates forces that act only within distances less …