Wen Jing, Wang Peiyi, Smith Sumona V, Haller Carolyn A, Chaikof Elliot L
Department of Surgery, Emory University, Atlanta, GA 30322, USA.
J Vasc Surg. 2007 Nov;46(5):1014-25. doi: 10.1016/j.jvs.2007.06.022. Epub 2007 Oct 1.
The syndecan family of cell surface proteoglycans can bind and modulate the activity of a diverse group of soluble and insoluble ligands, which have been shown to modulate events relevant to acute tissue repair and chronic injury responses. The expression of members of the syndecan family of heparan sulfate proteoglycans during the course of aortic aneurysm formation has not been previously investigated. In this investigation, the spatiotemporal expression of syndecan-1, -2, and -4 was characterized in a murine model of aneurysm formation.
ApoE-deficient mice were maintained on an atherogenic diet for 8 weeks with concurrent infusion of angiotensin II (0.75 mg/kg/day SQ). The expression of syndecan-1, -2, and -4 at the site of aneurysm formation was characterized by immunohistochemical staining and colocalization determined by double fluorescent immunostaining. Correlative examination was performed on tissue specimens harvested from patients at the time of open aneurysm repair.
In the aortic wall of age-matched, untreated mice, syndecan-4 was localized to the smooth muscle cells of the media. However, neither syndecan-1 nor syndecan-2 could be detected. Within 1 week of initiating a high fat diet and infusion of angiotensin II, syndecan-1 was abundantly expressed in infiltrating macrophages, predominantly localized to the periadventitial aorta. The expression of macrophage-associated syndecan-1 was accentuated during the course of aneurysm formation. As the aneurysm matured, syndecan-2 was abundantly expressed within the aortic thrombus and heterogeneous syndecan-4 staining noted within the aortic media. Significantly, abundant syndecan-1 positive macrophages were observed in explanted human specimens.
Given the established functional properties of this family heparan sulfate proteoglycans, chronically accelerated macrophage syndecan-1 shedding could generate a sustained proinflammatory, proteolytic, growth-stimulating environment. As a component of a counterbalancing reparative process, cell surface syndecan-2 may assist in TGF-beta mediated responses to limit the growth of abdominal aortic aneurysms.
细胞表面蛋白聚糖的syndecan家族能够结合并调节多种可溶性和不溶性配体的活性，这些配体已被证明可调节与急性组织修复和慢性损伤反应相关的事件。硫酸乙酰肝素蛋白聚糖的syndecan家族成员在主动脉瘤形成过程中的表达此前尚未得到研究。在本研究中，在动脉瘤形成的小鼠模型中对syndecan-1、-2和-4的时空表达进行了表征。
载脂蛋白E缺陷小鼠在致动脉粥样硬化饮食下饲养8周，同时输注血管紧张素II（0.75 mg/kg/天，皮下注射）。通过免疫组织化学染色表征动脉瘤形成部位的syndecan-1、-2和-4的表达，并通过双重荧光免疫染色确定共定位。对开放动脉瘤修复时从患者身上采集的组织标本进行相关检查。
在年龄匹配的未治疗小鼠的主动脉壁中，syndecan-4定位于中膜的平滑肌细胞。然而，未检测到syndecan-1和syndecan-2。在开始高脂肪饮食和输注血管紧张素II的1周内，syndecan-1在浸润的巨噬细胞中大量表达，主要定位于主动脉外膜周围。巨噬细胞相关的syndecan-1的表达在动脉瘤形成过程中加剧。随着动脉瘤成熟，syndecan-2在主动脉血栓中大量表达，并且在主动脉中膜内观察到syndecan-4染色不均一。值得注意的是，在移植的人体标本中观察到大量syndecan-1阳性巨噬细胞。
鉴于该硫酸乙酰肝素蛋白聚糖家族已确定的功能特性，慢性加速的巨噬细胞syndecan-1脱落可能产生持续的促炎、蛋白水解、生长刺激环境。作为平衡修复过程的一个组成部分，细胞表面syndecan-2可能有助于转化生长因子-β介导的反应，以限制腹主动脉瘤的生长。
