Linares A, Perales S, Palomino-Morales R J, Castillo M, Alejandre M J
Department of Biochemistry and Molecular Biology, Faculty of Sciences, University of Granada, Fuentenueva s/n, Granada, Spain.
Cardiovasc Hematol Disord Drug Targets. 2006 Sep;6(3):151-68. doi: 10.2174/187152906778249545.
Contractile-state smooth muscle cells (SMC), the only cell type in the arterial media, undergoes migration to the intima, proliferation, and abundant extracellular matrix production during the early stages of atherosclerosis. This involves the ingestion of low-density lipoprotein (LDL) and modified or oxidised LDL by macrophages together with SMC by several pathways including a scavenger pathway leading to accumulation of cholesterol esters and formation of foam cells. High-plasma cholesterol levels constitute a major causative risk for atherosclerosis. The membrane-bound transcription factor called sterol regulatory element binding protein (SREBP) activates gene-encoding enzymes of cholesterol and fatty acid biosynthesis. The SREBP expression, in response to diet, shows that are involved in both lipogenesis and cholesterol homeostasis, moreover SREBPs are regulated directly by cholesterol. Animal models were used in trials of atherosclerosis, and cholesterol feeding has been described elsewhere as producing atherosclerotic lesions. We have examined the morphological, molecular and proliferative change in arterial SMC mimicking such a cholesterol diet, this transformed SMC is a good model to study the alterations of the differentiated state of SMC, and the transformation into foam cell, caused by cholesterol-rich diet. Despite the complexity of the interactions in atherosclerosis, there are many opportunities to affect the homeostatic balance of the artery wall at SMC levels. We have considered here some of the possible targets for intervention with promising strategies for the nutritional control of the genes, and, in a general way, the possibilities for modulating the expression of genes influencing atherosclerosis.
收缩状态的平滑肌细胞（SMC）是动脉中层唯一的细胞类型，在动脉粥样硬化早期会迁移至内膜、增殖并大量产生细胞外基质。这涉及巨噬细胞与SMC通过多种途径摄取低密度脂蛋白（LDL）以及修饰或氧化的LDL，其中包括导致胆固醇酯积累和泡沫细胞形成的清道夫途径。高血浆胆固醇水平是动脉粥样硬化的主要致病风险因素。名为固醇调节元件结合蛋白（SREBP）的膜结合转录因子可激活编码胆固醇和脂肪酸生物合成的酶的基因。SREBP的表达受饮食影响，表明其参与脂肪生成和胆固醇稳态，此外，SREBP直接受胆固醇调节。动物模型被用于动脉粥样硬化试验， elsewhere as producing atherosclerotic lesions（此处原文有误，推测可能是“elsewhere as producing atherosclerotic lesions has been described”之类的表述，暂按现有错误翻译为“在其他地方已描述胆固醇喂养会产生动脉粥样硬化病变”）。我们研究了模拟这种胆固醇饮食时动脉SMC的形态、分子和增殖变化，这种转化的SMC是研究SMC分化状态改变以及由富含胆固醇的饮食导致其转化为泡沫细胞的良好模型。尽管动脉粥样硬化中的相互作用很复杂，但在SMC水平上有许多机会影响动脉壁的稳态平衡。我们在此考虑了一些可能的干预靶点以及有前景的基因营养控制策略，总体而言，还考虑了调节影响动脉粥样硬化的基因表达的可能性。
