Morel Sandrine, Kwak Brenda R
Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.
Methods Mol Biol. 2013;1037:381-98. doi: 10.1007/978-1-62703-505-7_22.
Atherosclerosis is an arterial progressive disease characterized by accumulation of lipids, macrophages, T lymphocytes, and smooth muscle cells in large- and medium-sized arteries. Erosion and rupture of the atherosclerotic plaque may induce myocardial infarction and cerebrovascular accidents that are responsible for a large percentage of sudden death. Atherosclerosis is often treated by angioplasty generally followed by stent implantation. Although angioplasty and stent implantation are necessary for the survival of the patient, they induce a trauma in the vessel wall that favors a vascular reaction called restenosis and the associated de-endothelialization increases the risk of thrombosis. To study mechanisms involved in restenosis and thrombus formation, animal models have been developed. In this chapter, we describe the experimental model of balloon injury adapted for mice and apply it to study the role of Cx43 in this process. Connexins are members of a large family of transmembrane proteins that allow exchange of ions and small metabolites between cytosol and extracellular space or between neighboring cells. Connexins are important in vascular physiology, they support radial and longitudinal cell-to-cell communication in the vascular wall, and have been shown to modulate vascular pathologies such as atherosclerosis and hypertension. We also describe the various connexin-specific tools, for example, transgenic mice, blocking peptides, antisense, and siRNA, and their value in obtaining insight into the role of Cx43 in restenosis and thrombus formation after vascular injury.
动脉粥样硬化是一种动脉进行性疾病，其特征是脂质、巨噬细胞、T淋巴细胞和平滑肌细胞在大中型动脉中积聚。动脉粥样硬化斑块的侵蚀和破裂可能诱发心肌梗死和脑血管意外，这些是导致很大比例猝死的原因。动脉粥样硬化通常通过血管成形术治疗，一般随后进行支架植入。尽管血管成形术和支架植入对患者的生存是必要的，但它们会在血管壁上造成创伤，从而引发一种称为再狭窄的血管反应，并且相关的内皮剥脱会增加血栓形成的风险。为了研究再狭窄和血栓形成所涉及的机制，已经建立了动物模型。在本章中，我们描述了适用于小鼠的球囊损伤实验模型，并将其应用于研究Cx43在此过程中的作用。连接蛋白是一大类跨膜蛋白的成员，它们允许离子和小代谢物在细胞质和细胞外空间之间或相邻细胞之间交换。连接蛋白在血管生理学中很重要，它们支持血管壁内的径向和纵向细胞间通讯，并且已被证明可调节诸如动脉粥样硬化和高血压等血管疾病。我们还描述了各种连接蛋白特异性工具，例如转基因小鼠、阻断肽、反义核酸和小干扰RNA，以及它们在深入了解Cx43在血管损伤后再狭窄和血栓形成中的作用方面的价值。
