The extracellular matrix on atherogenesis and diabetes-associated vascular disease
The extracellular matrix on atherogenesis and diabetes-associated vascular disease
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DOI：
10.1016/s1567-5688(01)00005-8
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发表时间：
2002-05-01
影响因子：
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通讯作者：
Bondjers, G
中科院分区：
文献类型：
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作者：
Camejo, G;Olsson, U;Bondjers, G
2 型糖尿病中动脉粥样硬化显着增加，这表明胰岛素抵抗 (IR) 和糖尿病的代谢紊乱会增强导致动脉病变的机制。多项研究表明，动脉内膜细胞外基质中发生的过程可能是共同致病机制的一部分。内膜细胞外基质是动脉粥样硬化发生的地方。该层含有纤维状大分子，如胶原蛋白、蛋白聚糖 (PG)、透明质酸和细胞外多域蛋白。 apoB-100 脂蛋白的赖氨酸、富含精氨酸的片段、LDL、IDL 和 Lp (a) 与 PG 的带负电荷的糖胺聚糖 (GAG) 发生特异性相互作用，导致脂蛋白滞留，这是动脉粥样硬化形成的起始过程之一。这种相互作用导致脂蛋白的脂质和蛋白质部分发生结构修饰，这似乎增加了它们对蛋白酶、磷脂酶和自由基介导的过程的敏感性。 apoB 脂蛋白，特别是小而密的 LDL，与内膜 PG 的结合增加了巨噬细胞和人动脉平滑肌细胞 (HASMC) 的摄取，导致“泡沫细胞”形成。在体外，非酯化脂肪酸（NEFA）水平升高会改变内皮细胞基底膜的基质，使其对大分子更具渗透性。 NEFA 导致控制 HASMC 分泌的 PG 组成的基因表达发生变化，从而形成对 LDL 具有高亲和力的基质。这些结果使我们推测，IR 和 2 型糖尿病血脂异常的一个重要组成部分，即慢性高 NEFA，可能会导致细胞改变，从而导致动脉内膜细胞外基质的变化。这种变化可能会增加内膜中保留的apoB脂蛋白的致动脉粥样硬化性，并导致在IR和2型糖尿病中经常观察到的动脉壁的全身性改变。 (C) 2002 Elsevier Science Ireland Ltd. 保留所有权利。
Atherosclerosis is remarkably increased in type 2 diabetes suggesting that mechanisms causing arterial lesion are enhanced by the metabolic disturbances of insulin resistance (IR) and diabetes. Several lines of research suggest that processes taking place in the arterial intima extracellular matrix may be part of a shared pathogenic mechanism. The intima extracellular matrix is where atherogenesis takes place. This layer contains fibrilar macromolecules like collagens, proteoglycans (PGs), hyaluronate, and extracellular multi-domain proteins. Specific interaction of lysine, arginine-rich segments of the apoB-100 lipoproteins, LDL, IDL and Lp (a), with the negatively charged glycosaminoglycans (GAGs) of PGs cause retention of the lipoproteins, one of the initiation process of atherogenesis. Such interactions cause structural modifications of the lipid and protein moieties of the lipoproteins that appear to increase their susceptibility to proteases, phospholipases and free radical-mediated processes. The association of apoB-lipoproteins, specially small and dense LDL, with intima PGs increases their uptake by macrophages and human arterial smooth muscle cells (HASMC) leading to `foam cell' formation. In vitro, elevated levels of non-esterified fatty acids (NEFA) alter the matrix of endothelial cells basement membrane making them more permeable to macromolecules. NEFA cause changes in the expression of genes controlling the PGs composition of the PGs secreted by HASMC causing formation of a matrix with high affinity for LDL. These results lead us to speculate that an important component of the dyslipidemia of IR and type 2 diabetes, chronic high NEFA, may contribute to cellular alterations that cause changes of the arterial intima extracellular matrix. Such changes may increase the atherogenicity of the retention of apoB lipoproteins in the intima and contribute to the systemic alteration of the arterial wall frequently observed in IR and type 2 diabetes. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.