Mineral Surface in Calcified Plaque Is Like That of Bone

Abstract

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...

Lipids in biocalcification: contrasts and similarities between intimal and medial vascular calcification and bone by NMR

“…Calcifi cations judged to be predominantly medial from six different individuals were obtained from femoral arteries of diabetic patients after amputation. Intimal calcifi ed atherosclerotic plaque was pretreated with collagenase and elastase as described in detail in Duer et al ( 16 ). Calcifi ed medial vascular material was frozen at Ϫ 20 C as soon as possible after surgery and subjected to sodium hydroxide and sodium hypochlorite digestion (see below) without further treatment.…”

Contrasts between organic participation in apatite biomineralization in brachiopod shell and vertebrate bone identified by nuclear magnetic resonance spectroscopy

“…We have used 13 Cf 31 Pg REDOR to show that acidic GAGs are the molecules most strongly associated with the interface in bone [4], dentine [9], mineralized articular cartilage [5] and pathologically calcified atherosclerotic plaque [10]. The apparent ubiquity of the GAG -mineral association has led us to hypothesize that GAGs, with their diversity of polar and charged functional groups, have been naturally selected as widespread, if not universal, participants in calcium phosphate biomineralization.…”

Ultrastructure of Apatite Crystals Formed During Vascular Calcification in Humans

“…The causes and mechanisms of ectopic calcification, however, have not been fully elucidated as yet. As a result, pathological calcification, such as vascular calcification and fibrodysplasia ossificans progressiva, may be regulated by many possible contributing factors, and may occur in the same manner as bone calcification occurs after the conversion of soft tissue to hard tissue-forming cells, namely, osteoblasts or osteoblast-like cells [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] . Thus, mainly on the basis of in vitro results, differentiation of soft tissue into hard tissueforming cells is considered to be the primary cause of ectopic calcification.…”