Small D M
Department of Medicine, Housman Medical Research Center, Boston University School of Medicine, Massachusetts.
Arteriosclerosis. 1988 Mar-Apr;8(2):103-29. doi: 10.1161/01.atv.8.2.103.
This review summarizes the evidence that the physical properties of lipids which accumulate in the intima play major roles in the progression and regression of lesions of atherosclerosis. All of the three major classes of lipids that accumulate in lesions (phospholipids, cholesterol, and cholesterol esters) are water insoluble. Phospholipids and cholesterol esters are almost mutually insoluble, but cholesterol, a crystalline solid at 37 degrees C, has considerable solubility in phospholipid bilayers and cholesterol esters. In normal infant intima, cholesterol is solubilized by phospholipid membranes. During fatty streak development, groups of cells are stimulated to take up more cholesterol than they excrete. The excess cholesterol is biochemically converted to cholesterol ester, which separates as droplets to form foam cells. Some fatty streaks then undergo a transition to an intermediate lesion containing excess cholesterol which is carried in cholesterol-supersaturated membranes and droplets. When nucleation of this excess cholesterol occurs, it precipitates as crystals; their formation coincides with the onset of necrosis and plaque formation. The hallmark of plaque is the presence of inert cholesterol crystals. They appear to form from hydrolysis of the older deposits of cholesterol esters in the base of intermediate lesions. Thus, the lipids in plaques are stratified, with recently deposited cholesterol esters present in the luminal part of the intima and older deposits in the deeper regions. When plasma cholesterol is lowered below about 150 mg/dl, lipids are mobilized from lesions and regression gradually occurs. Early in the regression process, cholesterol esters are reduced at least partly by hydrolysis to yield cholesterol, some of which may crystallize and inhibit rapid regression. After prolonged periods of low plasma cholesterol, cholesterol esters and foam cells disappear and crystalline cholesterol gradually dissolves, leading to true regression.
本综述总结了内膜中积聚的脂质的物理性质在动脉粥样硬化病变进展和消退中起主要作用的证据。积聚在病变中的所有三大类脂质（磷脂、胆固醇和胆固醇酯）都不溶于水。磷脂和胆固醇酯几乎互不溶解，但胆固醇在37℃时为结晶固体，在磷脂双层和胆固醇酯中有相当的溶解度。在正常婴儿内膜中，胆固醇被磷脂膜溶解。在脂纹形成过程中，细胞群被刺激摄取比排出更多的胆固醇。过量的胆固醇通过生化转化为胆固醇酯，胆固醇酯以液滴形式分离形成泡沫细胞。然后一些脂纹会转变为含有过量胆固醇的中间病变，这些胆固醇存在于胆固醇过饱和的膜和液滴中。当这种过量胆固醇发生成核时，它会沉淀为晶体；晶体的形成与坏死和斑块形成的开始相吻合。斑块的标志是存在惰性胆固醇晶体。它们似乎是由中间病变底部较老的胆固醇酯沉积物水解形成的。因此，斑块中的脂质是分层的，最近沉积的胆固醇酯存在于内膜的腔部，较老的沉积物存在于更深的区域。当血浆胆固醇降至约150mg/dl以下时，脂质从病变中动员出来，逐渐发生消退。在消退过程早期，胆固醇酯至少部分通过水解减少，产生胆固醇，其中一些可能结晶并抑制快速消退。在血浆胆固醇长期处于低水平后，胆固醇酯和泡沫细胞消失，结晶胆固醇逐渐溶解，导致真正的消退。
