Retention and activation of blood-borne proteases in the arterial wall - Implications for atherothrombosis
Retention and activation of blood-borne proteases in the arterial wall - Implications for atherothrombosis
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DOI：
10.1016/j.jacc.2006.04.098
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发表时间：
2006-11-07
影响因子：
24
通讯作者：
Michel, Jean-Baptiste
中科院分区：
文献类型：
--
作者：
Houard, Xavier;Leclercq, Anne;Michel, Jean-Baptiste
所有形式的动脉粥样硬化的特征在于动脉壁破裂的风险，导致临床并发症。这涉及腹主动脉瘤（AAA）的中膜和外膜破裂以及易损动脉粥样硬化血栓斑块的内膜帽破裂。细胞外蛋白酶，包括金属蛋白酶、局部产生的纤溶酶和白细胞弹性蛋白酶，通过其基质降解特性是动脉粥样硬化进展的重要分子介质。AAA的病理演变与其相关附壁血栓的生物学有关。事实上，在有血栓内衬的血管段中，血管壁较薄，细胞外基质降解更严重，外膜炎症反应比无血栓的血管段更强。几条证据强调了血栓在AAA中的作用，血栓是血液传播的蛋白酶的储存库，将蛋白酶从管腔输送到病变血管。在狭窄性动脉粥样硬化中，以往和最近的研究都提供了证据，表明斑块内复发性斑块在病变向易损性的演变中起着主导作用。在这篇综述中，我们将蛋白酶转运和腹主动脉瘤附壁血栓激活以及狭窄动脉粥样硬化斑块内血栓激活的作用进行了比较。我们假设斑块内血栓将血源性蛋白酶输送到病变中，在血栓/血肿形成时，这些蛋白酶被保留并激活，从而显著促进其有害作用。
All forms of atheroma are characterized by a risk of arterial wall rupture leading to clinical complications. This involves medial and adventitial ruptures in abdominal aortic aneurysm (AAA) and intimal cap rupture in vulnerable atherothrombotic plaques. Extracellular proteases, including metalloproteinases, locally generated plasmin, and leukocyte elastase, are important molecular mediators of atheroma progression via their matrix degradation properties. The pathological evolution of AAA is linked to the biology of its associated mural thrombus. Indeed, in aneurysmal segments lined by a thrombus, the wall is thinner, the extracellular matrix more degraded, and the adventitial inflammatory response greater than in segments that are not. Several lines of evidence highlight the role of the thrombus, in AAA, as a reservoir of blood-borne proteases that conveys them from the lumen to the diseased wan. In stenosing atheroma, both previous and recent studies provide evidence that recurrent intraplaque hemorrhages play a dominant role in the evolution of the lesion toward vulnerability. In this review, we draw a parallel between the role of protease conveyance and activation of the mural thrombus in AAA and of intraplaque hemorrhages in stenosing atheroma. We hypothesize that intraplaque hemorrhages convey blood-borne proteases into lesions, where they are retained and activated upon thrombus/hematoma formation, thus contributing significantly to their deleterious action.