Robert L, Robert A M, Jacotot B
Université Paris 6, Centre de Recherche Bioclinique sur le Vieillissement, Groupe Hospitalier Charles Foix-Jean Rostand, Ivry sur Seine, France.
Atherosclerosis. 1998 Oct;140(2):281-95. doi: 10.1016/s0021-9150(98)00171-3.
This review proposes reinvestigation of a topic studied in the author's laboratory over the last decades concerning the age-dependent modifications of the vascular extracellular matrix (ECM) as related to atherogenesis and its recognized risk-factors: blood lipids, lipoproteins. Most salient previous results are confronted with recent publications in this field. Age-dependent modifications of the vascular wall discussed in this review include upregulation of elastolytic enzymes, demonstrated for the first time in the vascular wall in this laboratory, matrix biosynthesis and receptor function. The progressive deposition of lipids in elastic tissues as well as the addition of lipoproteins or lipids to cell and organ cultures were shown to modify matrix biosynthesis and upregulate elastase expression. Lipid-elastin interactions exhibit a great deal of specificity as shown by the nature and amount of lipids accumulating in elastin in vivo and in vitro. Recent epidemiological studies (the EVA study) enables the confrontation of blood lipid parameters with matrix related components (serum elastase and inhibitors, elastin peptides, fibronectin) in the same blood samples. The elastin laminin receptor present on vascular cells was shown to trigger NO dependent vasodilation, and downregulation of cholesterol synthesis. Both of these functions decrease or disappear with age except the upregulation of elastase release which is preserved and increased. Recent experiments extended these findings to T-lymphocytes present also in the atherosclerotic plaque. Finally several recent publications are analyzed which give more precision on the cellular mechanisms underlying the above-described modifications.
本综述提议对作者实验室在过去几十年中研究的一个主题进行重新研究，该主题涉及血管细胞外基质（ECM）随年龄的变化及其与动脉粥样硬化及其公认风险因素（血脂、脂蛋白）的关系。以往最显著的研究结果与该领域的最新出版物进行了对比。本综述中讨论的血管壁随年龄的变化包括弹性蛋白酶的上调（首次在本实验室的血管壁中得到证实）、基质生物合成和受体功能。弹性组织中脂质的逐渐沉积以及向细胞和器官培养物中添加脂蛋白或脂质被证明会改变基质生物合成并上调弹性蛋白酶的表达。脂质与弹性蛋白的相互作用表现出很大的特异性，这在体内和体外弹性蛋白中积累的脂质的性质和数量上得到了体现。最近的流行病学研究（EVA研究）使得能够在相同的血液样本中对比血脂参数与基质相关成分（血清弹性蛋白酶和抑制剂、弹性蛋白肽、纤连蛋白）。血管细胞上存在的弹性蛋白层粘连蛋白受体被证明可触发一氧化氮依赖性血管舒张，并下调胆固醇合成。随着年龄的增长，这两种功能都会减弱或消失，但弹性蛋白酶释放的上调会持续并增强。最近的实验将这些发现扩展到了动脉粥样硬化斑块中也存在的T淋巴细胞。最后，对最近的几篇出版物进行了分析，这些出版物对上述变化背后的细胞机制给出了更精确地阐述。
