动脉粥样硬化斑块形成机制

    动脉粥样硬化是由于动脉内膜下脂质沉积，继而有纤维组织增生，形成粥样硬化斑块，向管腔内突出，斑块增大融合或斑块发生溃疡，继发血栓形成、狭窄，甚至阻塞。

    内皮损伤是继发动脉粥样硬化的主要原因，由于各种主要危险因素最终都损伤动脉内膜，而粥样硬化病变的形成是动脉对内膜损伤作出的炎症纤维增生性反应的结果。

    正常的动脉内膜附有一层非常光滑的内皮细胞，管腔粗细均匀。动脉内膜受损可为功能紊乱或解剖损伤。在长期高脂血症的情况下，增高的脂蛋白中主要是氧化修饰的低密度脂蛋白(ox LDL）和胆固醇对动脉内膜造成功能性损伤，使内皮细胞和白细胞(单核细胞和淋巴细胞)表面特性发生变化，即黏附因子表达增加。单核细胞黏附在内皮细胞上的数量增多，并从内皮细胞之间移入内膜下成为巨噬细胞，通过清道夫受体吞噬oxLDL，转变为泡沫细胞形成最早的粥样硬化病变脂质条纹。巨噬细胞能氧化LDL、形成过氧化物和超氧化离子，还能合成和分泌多种细胞因子，在这些细胞因子的作用下，促使脂肪条纹演变为纤维脂肪病变，再发展为纤维斑块。

Initiation of atherosclerosis.

    The diagram shows a cross-section through a muscular artery depicting a classic trilaminar structure. The intima of normal arteries is composed of a single layer of endothelial cells overlying a subendothelial matrix that contains occasional resident smooth muscle cells. The underlying tunica media, separated from the intima by the internal elastic lamina, contains multiple layers of vascular smooth muscle cells. The adventitia, the outermost layer of the blood vessel, separated from the media by the external elastic lamina, is not depicted in this diagram. Circulating leukocytes adhere poorly to the normal endothelium under normal conditions. When the endothelium becomes inflamed, however, it expresses adhesion molecules that bind cognate ligands on leukocytes. Selectins mediate a loose rolling interaction of leukocytes with the inflammatorily activated endothelial cells. Integrins mediate firm attachment. Chemokines expressed within atheroma provide a chemotactic stimulus to the adherent leukocytes, directing their diapedesis and migration into the intima, where they take residence and divide. These steps are depicted in a left-to-right chronological sequence.