Vascular Remodeling Induced by Naturally Occurring Unsaturated Lysophosphatidic Acid In Vivo
Vascular Remodeling Induced by Naturally Occurring Unsaturated Lysophosphatidic Acid In Vivo
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DOI：
10.1161/01.cir.0000089374.35455.f3
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发表时间：
2003-10
期刊：
影响因子：
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通讯作者：
Kenji Yoshida;W. Nishida;Ken’ichiro Hayashi;Y. Ohkawa;Akira Ogawa;J. Aoki;H. Arai;K. Sobue
中科院分区：
文献类型：
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作者：
Kenji Yoshida;W. Nishida;Ken’ichiro Hayashi;Y. Ohkawa;Akira Ogawa;J. Aoki;H. Arai;K. Sobue
我们之前发现不饱和（16:1,18:1和18:2）而非饱和（12:0,14:0,16:0和18:0）溶血磷脂酸（LPAs）是血管平滑肌细胞（VSMC）去分化的有效因子。不饱和LPAs通过协调激活细胞外信号调节激酶（ERK）和p38丝裂原活化蛋白激酶（p38MAPK），强烈诱导VSMC去分化，导致VSMC的增殖和迁移。在这里，我们研究了18:1和18:0 LPAs（分别作为代表性的不饱和和饱和LPAs）对体内脉管系统的影响。方法与结果：用18:1或18:0 LPA短暂治疗大鼠颈总动脉（CCAs），并进行组织学和生化分析。18:1而不是18:0的LPA能诱导主要由新生内膜组成的血管重构。[3H]18:1 LPA掺入cca表明，血管壁存在足够数量的未代谢[3H]18:1 LPA诱导VSMC去分化。在体内18:1 lpa诱导的新内膜形成也依赖于ERK和p38MAPK的协同激活。与球囊损伤的cca不同，18:1 lpa处理的cca在组织学上与人类动脉粥样硬化动脉相似。结论：这是第一个证明天然存在的不饱和LPA在体内诱导血管重构中的作用的报告，并为新内膜形成提供了一种新的动物模型。
Background—We previously identified unsaturated (16:1, 18:1, and 18:2) but not saturated (12:0, 14:0, 16:0, and 18:0) lysophosphatidic acids (LPAs) as potent factors for vascular smooth muscle cell (VSMC) dedifferentiation. Unsaturated LPAs strongly induce VSMC dedifferentiation via the coordinated activation of the extracellular signal–regulated kinase (ERK) and p38 mitogen–activated protein kinase (p38MAPK), resulting in the proliferation and migration of dedifferentiated VSMCs. Here, we investigated the effects of 18:1 and 18:0 LPAs (as representative unsaturated and saturated LPAs, respectively) on the vasculature in vivo. Methods and Results—Rat common carotid arteries (CCAs) were treated transiently with 18:1 or 18:0 LPA and then examined by histological and biochemical analyses. The 18:1 but not 18:0 LPA potently induced vascular remodeling that was composed primarily of neointima. The incorporation of [3H]18:1 LPA into the CCAs revealed that a sufficient amount of unmetabolized [3H]18:1 LPA to induce VSMC dedifferentiation was present in the vascular wall. The 18:1 LPA–induced neointimal formation in vivo was also dependent on the coordinated activation of ERK and p38MAPK. Unlike balloon-injured CCAs, the 18:1 LPA–treated CCAs showed a histological similarity to human atherosclerotic arteries. Conclusions—This is the first report demonstrating a role for a naturally occurring unsaturated LPA in inducing vascular remodeling in vivo and provides a novel animal model for neointimal formation.