Angiotensin II infusion promotes ascending aortic aneurysms: attenuation by CCR2 deficiency in apoE-/- mice.
Angiotensin II infusion promotes ascending aortic aneurysms: attenuation by CCR2 deficiency in apoE-/- mice.
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DOI：
10.1042/cs20090372
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发表时间：
2010-03-09
期刊：
影响因子：
--
通讯作者：
Cassis LA
中科院分区：
文献类型：
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作者：
Daugherty A;Rateri DL;Charo IF;Owens AP;Howatt DA;Cassis LA
AngII（血管紧张素 II）通过多种机制（包括趋化性）诱导动脉粥样硬化和 AAA（腹主动脉瘤）。因此，我们确定了趋化因子受体CCR2（CC趋化因子受体2）的全身缺乏对这些疾病的影响。为了实现这一目标，CCR2+/+ 或 CCR2−/− 的 apoE（载脂蛋白 E）−/− 小鼠通过微型渗透泵注射生理盐水或 AngII（1000 ng·kg−1 体重·min−1）28 天。 CCR2 缺乏会显着减弱动脉粥样硬化和 AAA，与收缩压或血浆胆固醇浓度无关。在本研究过程中，我们还观察到 AngII 输注导致仅限于 apoE−/− 小鼠升主动脉区域的大面积扩张。大部分扩张区域的主动脉中膜增厚。在内侧增厚的区域，可以辨别出不同的弹性蛋白层。弹性蛋白层之间的距离从中膜的内膜到外膜呈梯度扩大。这种病理学在升主动脉前部区域的局限性区域有所不同，其中弹性蛋白断裂是局灶性的并且几乎是透壁的。注入AngII的小鼠升主动脉的所有区域都有弥漫性内侧巨噬细胞聚集。 CCR2 的缺乏极大地减弱了 AngII 诱导的升主动脉管腔扩张。这种新的升主动脉瘤模型的病理学与 AngII 诱导的动脉粥样硬化或 AAA 明显不同，但所有血管病理学均因 CCR2 缺陷而减弱。
AngII (angiotensin II) induces atherosclerosis and AAAs (abdominal aortic aneurysms) through multiple proposed mechanisms, including chemotaxis. Therefore, we determined the effects of whole-body deficiency of the chemokine receptor CCR2 (CC chemokine receptor 2) on these diseases. To meet this objective, apoE (apolipoprotein E)−/− mice that were either CCR2+/+ or CCR2−/−, were infused with either saline or AngII (1000 ng·kg−1 of body weight·min−1) for 28 days via mini-osmotic pumps. Deficiency of CCR2 markedly attenuated both atherosclerosis and AAAs, unrelated to systolic blood pressure or plasma cholesterol concentrations. During the course of the present study, we also observed that AngII infusion led to large dilatations that were restricted to the ascending aortic region of apoE−/− mice. The aortic media in most of the dilated area was thickened. In regions of medial thickening, distinct elastin layers were discernable. There was an expansion of the distance between elastin layers in a gradient from the intimal to the adventitial aspect of the media. This pathology differed in a circumscribed area of the anterior region of ascending aortas in which elastin breaks were focal and almost transmural. All regions of the ascending aorta of AngII-infused mice had diffuse medial macrophage accumulation. Deficiency of CCR2 greatly attenuated the AngII-induced lumen dilatation in the ascending aorta. This new model of ascending aortic aneurysms has pathology that differs markedly from AngII-induced atherosclerosis or AAAs, but all vascular pathologies were attenuated by CCR2 deficiency.