Smith E B
Am J Pathol. 1977 Mar;86(3):665-74.
Most plasma proteins appear to be present in intima at concentrations that are a linear function of molecular weight and concentration in the plasma. Thus low density lipoprotein (LDL) (molecular weight, 2 X 10(6)) has the greatest retention relative to its plasma concentration, whereas the relative retention of albumin is only 15% of the relative retention of LDL. This gives rise to the concept that "whole plasma" crosses endothelium, and the steady state concentrations reflect rates of egress of the macromolecules, which in turn depend on molecular sieving. Fibrinogen is a major plasma protein in intima in addition to LDL and albumin, and there are also substantial amounts of the protease inhibitors alpha2-macroglobulin and alpha1-antitrypsin. Intima also contains insoluble derivatives of plasma--extracellular cholesterol, both free and esterified, and fibrin. The balances of intact LDL/"deposited" cholesterol and of fibrinogen/fibrin are closely linked with intimal morphology. Fibrinogen and electrophoretically mobile LDL are increased about threefold in gelatinous lesions, whereas there are only slight rises in fibrin and deposited cholesterol. In the deep layers of fibrous plaques, fibrin is increased fivefold and cholesterol up to thirtyfold. In these lipid-rich layers, LDL is rapidly lost on incubation of tissue samples, but in some gelatinous lesions it first increases and only decreases on longer incubation, suggesting release of a previously immobilized lipoprotein fraction. This immobilized lipoprotein was investigated by subjecting tissue samples to immunoelectrophoresis to remove mobile LDL and tissue enzymes, followed by treatment of the tissue with enzyme and measurement of the lipoprotein released on fresh immunoelectrophoresis plates. Plasmin or a crude collagenase released large amounts of lipoprotein from samples of amorphous atheroma lipid. For all samples the amount of lipoprotein released was highly correlated with the accumulation of deposited cholesterol, suggesting that immobilization of LDL may be an intermediate step in the irreversible deposition of extracellular cholesterol. Plasmin is highly effective in releasing immobilized lipoprotein, and the concentration of immobilized lipoprotein is significantly correlated with the concentration of insoluble fibrin, suggesting that the lipoprotein may in some way be immobilized by fibrin.
大多数血浆蛋白似乎以与分子量和血浆浓度呈线性函数关系的浓度存在于内膜中。因此，低密度脂蛋白（LDL）（分子量为2×10⁶）相对于其血浆浓度具有最大的潴留率，而白蛋白的相对潴留率仅为LDL相对潴留率的15%。这就产生了“全血浆”穿过内皮的概念，稳态浓度反映了大分子的流出速率，而这又取决于分子筛分。除LDL和白蛋白外，纤维蛋白原是内膜中的一种主要血浆蛋白，并且还存在大量的蛋白酶抑制剂α2-巨球蛋白和α1-抗胰蛋白酶。内膜还包含血浆的不溶性衍生物——细胞外胆固醇，包括游离的和酯化的，以及纤维蛋白。完整的LDL/“沉积”胆固醇的平衡以及纤维蛋白原/纤维蛋白的平衡与内膜形态密切相关。在胶样病变中，纤维蛋白原和电泳可移动的LDL增加约三倍，而纤维蛋白和沉积胆固醇仅略有升高。在纤维斑块的深层，纤维蛋白增加五倍，胆固醇增加高达三十倍。在这些富含脂质的层中，组织样本孵育时LDL迅速丢失，但在一些胶样病变中，它首先增加，仅在较长时间孵育后才减少，这表明先前固定的脂蛋白部分被释放。通过对组织样本进行免疫电泳以去除可移动的LDL和组织酶，然后用酶处理组织并在新鲜的免疫电泳板上测量释放的脂蛋白，对这种固定的脂蛋白进行了研究。纤溶酶或粗制胶原酶从无定形动脉粥样硬化脂质样本中释放出大量脂蛋白。对于所有样本，释放的脂蛋白量与沉积胆固醇的积累高度相关，这表明LDL的固定可能是细胞外胆固醇不可逆沉积的中间步骤。纤溶酶在释放固定的脂蛋白方面非常有效，并且固定脂蛋白的浓度与不溶性纤维蛋白的浓度显著相关，这表明脂蛋白可能以某种方式被纤维蛋白固定。
