The role of caveolin in pathogenesis of arteriosclerosis

小泡蛋白是小泡的主要成分，小泡是质膜的烧瓶状内陷，在跨膜信号转导中起重要作用。该分子作为内皮型一氧化氮合酶（eNOS）的内源性负调节因子。最近，小窝蛋白被认为与细胞增殖的抑制调节有关。本研究探讨了小窝蛋白和eNOS在动脉增生性病变中的表达。我们发现血管紧张素原基因敲除（Atg-/-）小鼠出现肾动脉硬化样病变，尤其是小叶间动脉和传入小动脉病变。在这些病变中，小窝蛋白过度表达，而eNOS表达强烈抑制。盐负荷（4% NaCl） 10 d后，小窝蛋白表达量显著降低，eNOS表达量显著增加。Hydralazine处理几乎完全消除了高盐饮食对cavelin和eNOS表达的影响。在肝、心、脾、肺和骨骼肌等其他器官中没有发现这些变化。野生型小鼠在治疗过程中，小窝蛋白和eNOS的表达没有变化。采用达尔盐敏感大鼠作为增生性肾动脉硬化模型。盐负荷（8% NaCl饮食）18周后，dahl盐敏感大鼠肾阻力血管出现硬化改变。病变包括小窝蛋白的过度表达和eNOS活性的显著降低。另一方面，达尔盐耐药大鼠的肾脏血管没有任何变化。这些结果与小窝蛋白通过eNOS调控参与血管增生性改变的观点一致，特别是在肾素-血管紧张素系统受到抑制的情况下。

Caveolin is a major component of caveolae, flask-shaped invaginations of plasma membranes that play important roles in the transmembrane signal transduction. This molecule functions as an endogenous negative regulator of endothelial-type nitric oxide synthase (eNOS). Recently, caveolin has been implicated in the inhibitory regulation of cell proliferation. The present study investigated the expression of caveolin and eNOS in the arterial hyperplastic lesion. We found that angiotensinogen gene-knockout (Atg-/-) mice had renal arteriosclerosis-like lesion especially in the interlobular arteries and afferent arteriolesis. In these lesion, caveolin was overexpressed whereas eNOS expression was strongly suppressed. After 10-days salt loading (4% NaCl diet), caveolin expression was significantly decreased with an increase in eNOS expression. Hydralazine treatment almost completely abolished the effects of high-salt diet on cavelin and eNOS expression. These chnages were not found in other organs including liver, heart, spleen, lung, and skeletal muscles. Wild-type mice showed no changes in caveolin or eNOS expression during the treatment. A Dahl-salt sensitive rat was used as another model for hyperplastic renal arteriosclerosis. After 18-weeks of salt loading (8% NaCl diet), Dahl-salt sensitive rats showed sclerotic changes in the renal resistance vessels. The lesion inluded overexpression of caveolin and marked decreases in eNOS activity. On the other hand, Dahl-salt resistant rats did not show any changes in renal vasculature. These results were consistent with the idea that caveolin participates in vascular hyperplastic change through eNOS regulation especially in the condition where renin-angiotensinsystem is suppressed.