Endothelial injury: blood-vessel wall interactions.
Endothelial injury: blood-vessel wall interactions.
复制标题
内皮损伤：血管壁相互作用。
DOI：
10.1111/j.1749-6632.1982.tb25725.x
复制
发表时间：
1982
影响因子：
5.2
通讯作者：
Faggiotto,A
中科院分区：
文献类型：
--
作者：
Ross,R;Bowen-Pope,D;Raines,EW;Faggiotto,A
正如本书其他部分所讨论的，维持内皮完整性，包括结构和功能的完整性，是动脉粥样硬化损伤假说的关键因素。这一假说表明，内皮的功能能力可能在某种程度上被与动脉粥样硬化形成相关的各种因素改变，并且这种改变导致一系列细胞变化，最终导致病变的形成。因此，可以想象，尽管”内皮损伤”可能代表动脉粥样硬化形成过程中的共同特征，但慢性高胆固醇血症引起的损伤与吸烟、糖尿病、高血压、或其他已知与动脉粥样硬化风险增加相关的因素。对损伤的反应假说表明，无论内皮细胞发生什么变化，它们最终导致来自血液的至少两种细胞（血小板和单核细胞/巨噬细胞）与改变的内皮或内皮下结缔组织相互作用的机会。这些内皮变化也可能为血浆成分以不受控制的方式进入动脉壁提供机会，并且在低密度脂蛋白升高的情况下，可能导致脂质或脂质降解产物在动脉壁中沉积。该假说指出，受损动脉中的血小板相互作用和巨噬细胞相互作用提供了释放至少两种生长因子的潜在机会：血小板衍生生长因子（PDGF）3和巨噬细胞衍生生长因子（MDGF）4进入损伤部位的动脉壁。血小板衍生生长因子已在Boyden室实验中被证明对平滑肌细胞5和成纤维细胞具有趋化性。6 MDGF也可能具有趋化性。如果这在体内是真的，该假设表明，这些生长因子释放到动脉壁中可以提供平滑肌细胞从中膜被吸引到内膜中的机会，并经历增殖反应，导致纤维肌弹性增殖性病变的发展，即纤维斑块，这是与动脉粥样硬化相关的典型病变的前驱病变。
As has been discussed elsewhere in this volume, maintenance of endothelial integrity, including both structural and functional integrity, represents a key element in the response to injury hypothesis of atherosclerosis. This hypothesis suggests that the functional capacity of the endothelium may in some way be altered by the various factors that are associated with atherogenesis, and that this alteration leads to a sequence of cellular changes that culminate in the formation of the lesions. 1, 2 It is conceivable, therefore, that although" endothelial injury" may represent a common denominator in the process of atherogenesis, the sequence of events may be somewhat different in injury resulting from chronic hypercholesterolemia versus that which may occur as a result of cigarette smoking, diabetes, hypertension, or other factors that are known to be associated with an increased risk of atherosclerosis.The response to injury hypothesis suggests that whatever the changes in the endothelial cells, they ultimately lead to opportunities for interactions of at least two cells from the blood, the platelet and the monocytelmacrophage, with either the altered endothelium or the subendothelial connective tissue. These endothelial changes could also present opportunities for entry of constituents of the plasma into the artery wall in an uncontrolled fashion and, in the case of elevated low-density lipoproteins, may lead to the deposition of lipids or degradation products of lipids in the artery wall. The hypothesis states that platelet interactions and macrophage interactions in an injured artery provide potential opportunities for release of at least two growth factors: the platelet-derived growth factor (PDGFJ3 and the macrophage-derived growth factor (MDGF), 4 into the artery wall at sites of injury. The platelet-derived growth factor has been demonstrated in Boyden chamber experiments to be chemotactic for smooth muscle cells5 and fibroblasts. 6 It is also possible that MDGF may be chemotactic. If this were true in vivo, the hypothesis suggests that the release of these growth factors into the artery wall could provide opportunities for smooth muscle cells to be attracted from the media into the intima, and to undergo a proliferative response that would lead to the development of a fibromusculoelastic proliferative lesion, a precursor lesion to those classically associated with atherosclerosis, namely the fibrous plaque.