Characteristic localisation of denatured high-density lipoprotein (HDL) at the periphery of a lipid core in human atherosclerotic lesions

Aims: High-density lipoprotein (HDL) has been reported to efflux cholesterol (Chl) from the cell membrane, and the physiological balance between the influx and efflux of Chl is important in the formation of atherosclerotic lesions. Methods: In order to clarify these mechanisms in atherosclerotic lesions, the ratios of areas of apoprotein A-I (apo A-I)-positive areas were determined using a fluorescence polarisation microscope coupled to a spectrometer. Results: According to the staining patterns of apo A-I, atherosclerotic lesions are classified into three types, namely, focal dense area (FA), diffuse dense area (DA) and shading area (SA). In FA, protein was prominent and lipid was minimal in the intercellular space of degenerated cells in the thickened intima. In DA, the protein and lipid were co-localised. In SA at the periphery of lipid core, more lipids were present than protein. In the developed lesions, FA and SA were statistically bigger than those in the early lesions. Conclusions: These results suggest that an effective micro-solubilisation mechanism in FA may result in a low lipid content. Moreover, accumulated HDL may alter the relationship between various lipid vesicles and crystals in the extracellular matrix, and be an additional factor for the fragility of atheromatous plaques at the periphery of the lipid core.