Objectives-Cell biological studies demonstrate remarkable similarities between mineralization processes in bone and vasculature, but knowledge of the components acting to initiate mineralization in atherosclerosis is limited. The molecular level microenvironment at the organic-inorganic interface holds a record of the mechanisms controlling mineral nucleation. This study was undertaken to compare the poorly understood interface in mineralized plaque with that of bone, which is considerably better characterized. Methods and Results-Solid state nuclear magnetic resonance (SSNMR) spectroscopy provides powerful tools for studying the organic-inorganic interface in calcium phosphate biominerals. The rotational echo double resonance (REDOR) technique, applied to calcified human plaque, shows that this interface predominantly comprises sugars, most likely glycosaminoglycans (GAGs). In this respect, and in the pattern of secondary effects seen to protein (mainly collagen), calcified plaque strongly resembles bone. Conclusion-The similarity between biomineral formed under highly controlled (bone) and pathological (plaque) conditions suggests that the control mechanisms are more similar than previously thought, and may be adaptive. It is strong further evidence for regulation of plaque mineralization by osteo/chondrocytic vascular smooth muscle cells. Key Words: atherosclerosis Ⅲ biomineralization Ⅲ glycosaminoglycans Ⅲ nuclear magnetic resonance spectroscopy Ⅲ vascular calcification C alcification 1 is prevalent in numerous vascular pathologies and is associated with adverse clinical outcomes. Parallels have frequently been drawn between ectopic calcification processes in vessels and normal developmental osteogenesis. In fact vascular calcified material is by many criteria indistinguishable from bone, and its formation involves the participation of many cellular and molecular signaling processes underlying normal osteogenesis. 2 These include matrix vesicle release, expression of mineralizationregulating proteins by vascular smooth muscle cells (VSMCs) of the vessel wall, and the association of calcification with lipid and chronic inflammation, a hallmark of atherosclerosis. 3 Indeed vascular calcification is recognized as regulated biomineralization instead of merely passive precipitation. However questions are still unanswered concerning the mechanisms leading to the initiation of calcification in the vessel wall particularly as it occurs in different vascular environments (ie, media and intima), which do not mimic that of bone. Moreover, VSMCs can overexpress mineralization inhibitors such as matrix Gla protein (MGP) to effectively block mineralization. 4 Aspects of the molecular structure of mineralized tissues 5 can be studied by the solid state NMR (SSNMR) technique 13 C{ 31 P} rotational echo double resonance (REDOR). 6 13 C is a stable, nonradioactive, NMR-receptive isotope of carbon occurring naturally at about 1.1% abundance; similarly 31 P is a stable NMR-receptive isotope of phosphorus which however is natu...