Organculture as a new model of atherosclerosis

本研究旨在建立一种新的血管粥样硬化实验模型。为此，我们使用了血管器官培养系统，而不是培养内皮细胞，后者具有更好地保存组织结构、细胞间相互作用、细胞外基质以及分化细胞的形态和功能的条件，从而可重复地研究整个组织在环境刺激下的行为。我们测试了白细胞介素- 1b、胎牛血清（FBS）和血小板衍生生长因子（PDGF）这三种被认为与血管生长相关疾病有关的药物的作用。所得结果如下：1)我们首先证明了白细胞介素- 1b通过no依赖和独立的机制放松血管平滑肌（Takizawa et aI）。:欧元。J.Pharmacol。33: 143-150, 1997)。至于no无关的机制，我们进一步揭示了atp敏感的K通道激活引起的膜超极化可能是部分原因。2) FBS慢性治疗可显著降低兔肠系膜动脉内皮no依赖性松弛。内皮NO合成酶的总mRNA也减少。PDGF与FBS的效果相似。上述结果提示，家兔肠系膜动脉生长激活可降低内皮NO合成酶mRNA，减少NO的产生，损害内皮依赖性松弛。这些结果表明，器官培养是研究血管生长相关疾病机制的有效方法。

The purpose of this study is to develop new experimental model of a vascular atherosclerosis. For this purpose, we utilized a vascular organ culture system, rather than cultured endothelial cells, which has the advantages to obtain the conditions that better preserves tissue architecture, cell-to-cell interactions, the extracellular matrix, and the morphology and function of differentiated cells and thereby to reproducibly study behavior of the whole tissue in response to environmental stimuli. We tested the effect of tnree agents, interleukin-1B, fetal bovine serum (FBS) ana platelet derived growth factor (PDGF), which are assumed to be related to the vascular growth related disease. The results obtained are follows.1) We first demonstrated that Interleukin-1B relaxes vascular smooth muscle by the NO-dependent and independent mechanisms (Takizawa et aI. : Eur. J.Pharmacol. 330 : 143-150, 1997). As for the NO-independent mechanism, we further revealed that membrane hyperpolarization due to activation of ATP-sensitive K channels may partly be responsible for it.2) Chronic treatment with FBS markedly decreased the endothelial NO-dependent relaxation in rabbit mesenteric artery. Total mRNA for endothelial NO synthase were also reduced. PDGF showed similar results with FBS.These results suggest that growth activation of rabbit mesenteric artery decreases endothelial NO synthase mRNA, reduces NO production and impairs endothelium-dependent relaxation.These results suggest that organ culture is a useful method for studying the mechanism ofvascular growth related disease.