Deposition Patterns and Localization of Apolipoprotein A1 and Their Relation to Plaque Morphology in Human Coronary Artery

Backgrounds: Besides comprising high-density lipoprotein (HDL), apolipoprotein A1 (ApoA1) itself acts as an anti-atherogenic substance but its supplying routes and localization in the human coronary artery wall is poorly understood. The present study was performed to clarify supply route(s) and localization of ApoA1 and its relation to human coronary plaque morphology. Methods: Using 36 coronary arteries obtained from 15 autopsy subjects, deposition patterns of ApoA1 and whether it is conveyed by CD68 (+)-macrophage or vasa vasorum, and whether apoA1 co-localized with HDL were examined immunohistochemically. Also, the relationship between localization of ApoA1 and plaque morphology that was classified by angioscopy and histology was examined. Results: ApoA1 was deposited in a dotted or diffuse pattern in the coronary plaques. The dotted pattern represented ApoA1 carried by CD68 (+)-macrophages and diffuse pattern by vasa vasorum. The percentage (%) incidence of ApoA1 increased in the order of normal segments, white plaques (growth stage) and yellow plaques (mature stage). ApoA1 was also observed in the pericoronary adipose tissue (PCAT), and ApoA1-containing CD68 (+)-macrophages were observed not only in the intima (plaques) but also in the media, adventitia and PCAT. ApoA1 did not necessarily co-localize with HDL. Conclusions: The findings suggested that ApoA1 was conveyed to coronary plaques either by CD68 (+) -macrophages or vasa vasorum from the adventitia (possibly PCAT) and that ApoA1 began to deposit with plaque growth and increasingly deposited in mature stage of plaques. Accordingly, externally administered ApoA1-mimetics after plaque maturation may not be accepted by the plaques and fail to prevent coronary events. One possible way of making ApoA1-mimetics effective in preventing coronary events, is to administer them before plaque maturation.