Palombo D, Maione M, Cifiello B I, Udini M, Maggio D, Lupo M
Department of Cardiac and Vascular Diseases, Mauriziano Umberto I Hospital, Turin, Italy.
J Cardiovasc Surg (Torino). 1999 Apr;40(2):257-60.
The main chronic degenerative diseases of the abdominal aorta, namely aneurysmatic and steno-obstructive pathologies, have a common denominator: atherosclerosis. Both pathologies are characterised by the destruction of the structural integrity of the extracellular protein matrix (ME). A number of studies have shown the presence and involvement of a group of enzymes with proteolytic activity towards one or more ME components, the matrix metalloproteinases (MMPs), in the pathogenesis of aneurysms of the abdominal aorta. Other authors have underlined the role of MMPs in the proliferation and migration process of smooth muscle cells into the intima in the pathogenesis of atheromasic plaque. The aim of this study was to evaluate the possible role of these enzymes in the pathogenesis of chronic degenerative diseases of the aorta.
Fragments of aortic wall were removed from patients undergoing elective aortic surgery for aneurysms (14 patients) or aortic steno-obstruction (4 patients). The samples obtained were treated appropriately and then subject to immunohistochemical analysis. The preparations were incubated with specific anti-MMP antibodies and were also incubated with substrate and chromogen, forming a pigmented precipitate on the site of the antigen, before being observed using an optic microscopic at an enlargement of 250x. Nuclear positivity linked to the presence of the antigen testified the validity of staining. Lastly, the MMP INDEX, or in other words the number of positive cells out of 100, was stained in the adventitia and in the tunica media in each preparation.
MMPs were divided into three main groups: interstitial collagenase (MMP1) which degrade type I and III native collagen; gelatinases (MMP9, MMP2) which act on elastin and type IV collagen; stromelysins (MMP3) with specific proteolytic action towards proteoglycans, fibronectin and laminine. In our experience, those preparations obtained from aorta affected by steno-obstructive pathologies (4 patients) revealed the presence of MMPs with a preferential localisation on the intimal side of the tunica media. In particular, the increased activity of gelatinases MMP9 in atherosclerotic aorta might be responsible for destroying the internal elastic lamina and fostering the proliferation and migration of smooth muscle cells and the formation of atheromasic plaque. On the other hand, preparations obtained from aneurysmatic aorta (14 patients) showed an opposite situation with a preferential localisation within the adventitia and on the adventitial side of the media. Above all, the loss of elastin represents an essential stage in the formation of aortic aneurysms.
This study concords with numerous authors who have demonstrated the involvement of proteinase MMPs in the development of aortic aneurysms and their possible role in the pathogenesis of atheromasic plaque. The different origin of these enzymes (inflammatory cells and macrophages or endothelial cells) may be the result of different pathogenetic mechanisms. Although they present different pathogenetic features, aortic aneurysms and steno-obstructions have a common denominator in atherosclerosis. The mechanisms responsible for their evolution towards one or other form are not known. The different expression of MMPs in the context of the aortic wall represents a field for future research.
腹主动脉的主要慢性退行性疾病，即动脉瘤性和狭窄阻塞性病变，有一个共同特征：动脉粥样硬化。这两种病变的特点都是细胞外蛋白质基质（ME）的结构完整性遭到破坏。多项研究表明，一组对一种或多种ME成分具有蛋白水解活性的酶，即基质金属蛋白酶（MMPs），在腹主动脉瘤的发病机制中存在并发挥作用。其他作者强调了MMPs在动脉粥样硬化斑块发病机制中平滑肌细胞增殖和向内膜迁移过程中的作用。本研究的目的是评估这些酶在主动脉慢性退行性疾病发病机制中的可能作用。
从因动脉瘤（14例患者）或主动脉狭窄阻塞（4例患者）接受择期主动脉手术的患者身上获取主动脉壁碎片。对获得的样本进行适当处理，然后进行免疫组织化学分析。将制剂与特异性抗MMP抗体孵育，还与底物和显色剂孵育，在抗原部位形成有色沉淀，然后用光学显微镜在250倍放大倍数下观察。与抗原存在相关的核阳性证明了染色的有效性。最后，在每个制剂的外膜和中膜中对MMP指数，即每100个阳性细胞的数量进行染色。
MMPs分为三大类：间质胶原酶（MMP1），可降解I型和III型天然胶原；明胶酶（MMP9、MMP2），作用于弹性蛋白和IV型胶原；基质溶解素（MMP3），对蛋白聚糖、纤连蛋白和层粘连蛋白具有特异性蛋白水解作用。根据我们的经验，从受狭窄阻塞性病变影响的主动脉（4例患者）获得的那些制剂显示存在MMPs，其优先定位在中膜的内膜侧。特别是，动脉粥样硬化主动脉中明胶酶MMP9活性的增加可能是破坏内弹性膜、促进平滑肌细胞增殖和迁移以及形成动脉粥样硬化斑块的原因。另一方面，从动脉瘤性主动脉（14例患者）获得的制剂显示出相反的情况，优先定位在外膜内和中膜的外膜侧。最重要的是，弹性蛋白的丧失是主动脉瘤形成的一个关键阶段。
本研究与众多作者一致，他们证明了蛋白酶MMPs参与主动脉瘤的发展及其在动脉粥样硬化斑块发病机制中的可能作用。这些酶的不同来源（炎症细胞和巨噬细胞或内皮细胞）可能是不同发病机制的结果。尽管主动脉瘤和狭窄阻塞具有不同的发病特征，但它们在动脉粥样硬化方面有一个共同特征。导致它们向一种或另一种形式演变的机制尚不清楚。MMPs在主动脉壁中的不同表达是未来研究的一个领域。
