Pathologic Study On The Relationship Between OxLDL,ABCA1, Apoptosis And Human Coronary Atherosclerotic Plaque Stabilization

Background and Purpose Rupture of coronary atherosclerotic plaque(especially vulnerable plaques)"and superimposed thrombosis are the events preceding the vast majority of acute coronary syndromes. It is believed that oxLDL is closely related to many factors resulting in plaque rupture such as apoptosis of SMCs, inhibition of ABCA1 and angiogenesis. However most studies about these were practised in animals or in cultured cell. The present study was designed to find out the relation between oxLDL and the stabilization of plaques in human coronary arteries and to investigate the role of oxLDL in creating vulnerable sites in atherosclerotic plaques.Materials and methods Specimens of coronary arteries were obtained at autopsy from 42 patient with acute coronary syndromes. Plaque morphology was evaluated by using hematoxylin and eosin stained slides. Then, 722 tissue blocks of late-stage lesions were classified into two groups as either unstable(n=82), in which the plaque characterized by a large extracellular lipid core (more than 40% of the plaque area)or stable(n=740),in which the lipid core was less than 40% of the plaque area. 40 blocks selected randomly from each group were immunohistochemicully investigated by using monoclonal and polyclonal antibodies against oxLDL, ABCA1, macrophage(CD68) , smooth muscle cell(SMA) , proapoptoticprotein (BAX), endothelial(F-VIII) and DNA in situ terminal deoxynucleotidyl transferase end-labeling (TUNEL). Computeraided plaimeter was used in quantitative analysis. Results 1. In unstable plaques, the ratios( %o )of immunoreactive positive areas of oxLDL were significantly increased than that in stable plaques and most oxLDL were located in the shoulder of the plaques. The lipid core was immunoreative region positive for oxLDL. 2. ABCA1 expressed higher in stable plaques than in unstable plaques. There was significantly negative relation between expression of ABCA1 and oxLDL (P<0. 01) . 3. There are more apoptotic SMCs in unstable plaques than in stable ones. Areas positive for oxLDL showed lower SMA immunoreactivity (P<0. 01). SMCs staining positive for oxLDL showed expression of BAX(P<0. 01), a proapoptotic protein of the BCL-2 family. There was significant positive relation between apoptosis of VSMCs and oxLI)L(F-BAX/oxLDL, F-TUNEL/oxLDL). 4. There was significantly positive relation between neovascularization and oxLDL(P<(). 01)Conclusions These findings suggest that oxLDL in coronary atherosclerotic plaque are closely associated with the decreased stabilization of the plaques. The inhibition of ABCA1 by oxLDL promote the.accumulation of the lipid which increase the vulnerability of the plaque. Apoptosis induced by oxLDI. results in the loss of SMCs and this may contribute to plaque instability and rupture. In addition, oxLDL at the side of unstable plaques may be a inducer of the influx ofinflammatory cell which could directly contribute to the decrease plaque stabilization.