CALCIFICATION IN ATHEROSCLEROTIC PLAQUE OF HUMAN CAROTID ARTERIES - ASSOCIATIONS WITH MAST-CELLS AND MACROPHAGES

Calcification has been examined in 250 samples of atherosclerotic lesi ons (types II to VI) of human carotid arteries using von Kossa and hae matoxylin staining. Early calcification described as 'stippling' was f irst noted in stage III specimens, with intermediate and solid calcifi cations becoming increasingly prominent within advanced plaques, espec ially stages Vb and Vf. Although the relative frequencies of stippling , intermediate and large calcified deposits varied between plaques of the same stage, the prevalent sites of calcification were recognized a s the deeper regions of the intima and the atheroma. Immunolocalizatio n and histochemical techniques were used to identify the associations of mast cells (MCs), macrophages, smooth muscle cells (SMCs), and elas tin with the different stages of calcification. Early, dispersed stipp ling was commonly associated with local accumulations of macrophages ( HAM56 and CD68-positive), MCs and extracellular MC tryptase, the prese nce of immunoreactive elastin, but the relative absence of SMCs. Inter mediate stages of calcification described as 'morula' deposits mere al so associated with local increases in the numbers of macrophages and M Cs. Larger calcified deposits, even within the same plaque specimen, s howed no regular pattern of cellular or elastin associations. However, in the vast majority of specimens, macrophages represented the predom inant cell, type associated with different phases of calcification. By contrast, the calcification less frequently observed in the media ben eath advanced plaques was commonly associated with SMCs and elastin; o nly rarely mere macrophages or MCs present. These studies are the firs t to demonstrate that macrophages, MCs, and extracellular tryptase fre quently occupy micro-environmental loci showing the first stages of ca lcification within the atherosclerotic plaque; similar associations wi th more advanced mineral deposits are discussed in relation to plaque rupture. (C) 1998 John Wiley & Sons, Ltd.