DUFF,GEORGE,LYMAN MEMORIAL LECTURE - PROGRESSION AND REGRESSION OF ATHEROSCLEROTIC LESIONS - INSIGHTS FROM LIPID PHYSICAL BIOCHEMISTRY
DUFF,GEORGE,LYMAN MEMORIAL LECTURE - PROGRESSION AND REGRESSION OF ATHEROSCLEROTIC LESIONS - INSIGHTS FROM LIPID PHYSICAL BIOCHEMISTRY
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DOI：
10.1161/01.atv.8.2.103
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发表时间：
1988-03-01
期刊：
影响因子：
--
通讯作者：
SMALL, DM
中科院分区：
文献类型：
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作者：
SMALL, DM
本文综述了脂质的物理性质在动脉粥样硬化病变的进展和消退中起重要作用的证据。在病变中积聚的所有三种主要类型的脂质（磷脂、胆固醇和胆固醇酯）都是水不溶性的。磷脂和胆固醇酯几乎互不溶，但胆固醇在37 ℃时为结晶固体，在磷脂双层和胆固醇酯中具有相当大的溶解度。在正常婴儿内膜中，胆固醇被磷脂膜溶解。在脂肪条纹发育过程中，细胞群受到刺激，吸收的胆固醇比排泄的多。过量的胆固醇被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。一些脂肪条纹然后经历过渡到含有过量胆固醇的中间病变，这些胆固醇携带在胆固醇过饱和的膜和液滴中。当这种过量胆固醇成核时，它沉淀为晶体;它们的形成与坏死和斑块形成的开始一致。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胆固醇酯的较老沉积物水解而形成的。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管腔部分，而较老的沉积物存在于较深的区域。当血浆胆固醇降低到低于约150 mg/dl时，脂质从病变中动员出来，并逐渐消退。在退化过程的早期，胆固醇酯至少部分地通过水解被还原以产生胆固醇，其中一些可以结晶并抑制快速退化。经过长时间的低血浆胆固醇，胆固醇酯和泡沫细胞消失，结晶胆固醇逐渐溶解，导致真正的回归。
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.