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一种诱导小鼠主动脉瘤的新方法。

A new procedure to induce aortic aneurysms in mice.

机构信息

Department of Physiology, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain; CIBER de Enfermedades Cardiovasculares, Madrid, Spain.

Research Support Unit, Hospital General Mancha Centro, Alcázar de San Juan, Spain; Health Research Institute of Castilla-La Mancha, IDISCAM, Tomelloso, Spain.

出版信息

Methods Cell Biol. 2024;188:61-71. doi: 10.1016/bs.mcb.2024.03.005. Epub 2024 May 31.

Abstract

Aortic aneurysms (AAs) are a major public health challenge, featured by a progressive impairs in aortic wall integrity that drives to aortic dilation and, in end stage, to its rupture. Despite important advances in the surgical treatment of aortic aneurysms, there is currently no pharmacological intervention that prevents their development, reduces their expansion, or avoids their rupture. In addition to classic risk factors such age or gender, several heritable connective tissue disorders have been associated with AA developing, highlighting the role of extracellular matrix (ECM) genes alterations in the developing of AA. In this sense, we have recently demonstrated that global deletion of the cellular communicating network factor 2 (CCN2), previously known as connective tissue growth factor (CTGF) due to its role in the extracellular matrix formation, predisposes to early and lethal AAs development after Angiotensin II (Ang II) infusion in mice. Here, we detail the protocol to induce and detect AAs generation in inducible global CCN2 knockout mice after Ang II infusion which allow the characterization of CCN role in AA development and may help to the development of pharmacological target for AA treatment.

摘要

主动脉瘤(AAA)是一个主要的公共健康挑战,其特征是主动脉壁完整性的进行性损害,导致主动脉扩张,并在晚期导致破裂。尽管在主动脉瘤的外科治疗方面取得了重要进展,但目前尚无药物干预措施可以预防其发生、减少其扩张或避免其破裂。除了年龄或性别等经典危险因素外,几种遗传性结缔组织疾病也与 AAA 的发生有关,这突出了细胞外基质(ECM)基因改变在 AAA 发生中的作用。在这方面,我们最近证明,细胞通讯网络因子 2(CCN2)的全局缺失(先前由于其在细胞外基质形成中的作用而称为结缔组织生长因子(CTGF))会导致 Angiotensin II(Ang II)在小鼠中输注后早期和致命的 AAA 发展。在这里,我们详细介绍了在 Ang II 输注后诱导和检测可诱导的全局 CCN2 敲除小鼠中 AAA 生成的方案,该方案允许对 CCN 在 AAA 发展中的作用进行特征描述,并可能有助于开发 AAA 治疗的药物靶点。

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