This study demonstrates the involvement of the MMP/TIMP system in ECM remodelling of both AS and AR. These findings provide evidence of inflammatory injury more severe in AS than in AR and involvement of mesenchymal cell response.

Objectives-The purpose of this study was to investigate whether thoracic ascending aortic aneurysm (TAAA) induces platelet activation as mural thrombus participates in aortic dilatation in abdominal aortic aneurysm and TAAA are associated with rheological factors favoring coagulation activation. Methods and Results-We studied the relation between coagulation activation and aortic diameter in Marfan patients (MFS) with various aortic diameters (nϭ52). We then studied patients presenting large aneurysms associated with bicuspid aortic valve (BAV) and degenerative form. Lastly, we used immunochemistry and biochemistry to investigate prothrombin/thrombin retention within the aortic wall. Microparticles, sGPV, tissue factor, and TAT complexes were increased in plasma from MFS with large aneurysms (Ն45 mm) compared to MFS with limited aortic dilatation (Ͻ45 mm). Similar elevations were observed in all patients with large aortic aneurysms, regardless of the etiology, the site of maximal aortic dilation, associated valvulopathy, risk factors, or treatments. P-selectin and platelet-bound fibrinogen were also increased, demonstrating platelet activation in large aneurysms. Significant increase in sCD146 plasma concentration suggested alteration of endothelium. Conclusions-Platelet activation occurs in patients with large aneurysms of the ascending aorta, is dependent on aortic dilation, and is associated with thrombin generation, part of which appears to be retained in mucoid degeneration areas. (Arterioscler Thromb Vasc Biol 2008;28:940-946)Key Words: thoracic aortic aneurysm Ⅲ coagulation Ⅲ Marfan Ⅲ platelets T horacic ascending aortic aneurysms (TAAA) are defined by an enlargement of the ascending aorta. TAAA can be observed in old patients without clear etiologic factors, in whom it represents a primary degenerative pathology of the ascending aorta. 1 But it can also occur in the younger population; it is then usually linked to a genetic or congenital disease. Marfan syndrome represents the majority of these cases. This is usually related to mutations in fibrillin1 2 and rarely to mutations in transforming growth factor (TGF)␤R 2, which can also be responsible for Loeys-Dietz Syndrome and familial aortic aneurysm. [3][4][5] Other molecular abnormalities have been implicated, such as mutations in myosin, 6 TGF␤R 1 , 5 ACTA2, 7 or other currently unknown genes. 8 Moreover, bicuspid aortic valves (BAV), which may be familial, 9 are associated with a high risk of aneurysm of the ascending aorta. 10 In contrast to their etiologic diversity, all localized aortic dilations share common rheological characteristics. In normal human aorta, the regular geometry (tubular shape and parallel walls) results in laminar blood flow and in a homogeneous shear rate, maintaining a physiological steady-state among the blood components and between the circulating blood and arterial wall. 11 Changes in arterial geometry considerably modify rheological parameters and therefore influence interactions between blood components. 11,12 The modu...