Sangiorgi Giuseppe, Trimarchi Santi, Mauriello Alessandro, Righini Paolo, Bossone Eduardo, Suzuki Toru, Rampoldi Vincenzo, Eagle Kim A
Department of Cardiovascular Diseases, Istituto Policlinico San Donato, University of Milan, Milan, Italy.
J Cardiovasc Med (Hagerstown). 2006 May;7(5):307-15. doi: 10.2459/01.JCM.0000223251.26988.c5.
Aortic dissection is characterized by an acute phase of medial dissection and a subacute-chronic phase of vessel wall repair. Matrix metalloproteinases (MMPs), through degradation of extracellular matrix, may play an important role in these processes. Elevation of MMPs might represent an opportunity to diagnostically characterize acute or chronic aortic processes. We examined the potential diagnostic role of MMP-9 and MMP-2 in different phases of aortic dissection.
Plasma levels of MMPs were evaluated by enzyme-linked immunosorbent assay technique in 13 patients affected by acute aortic dissection (nine type A, four type B). Ten healthy subjects were used as controls. In patients with type B aortic dissection treated medically, plasma curves (1, 3, 6, 12, 24, 48 and 96 h; 1 and 2 weeks; and 2 months from symptom onset) were also assessed. Aortic tissue samples obtained during surgery were evaluated by immunohistochemistry and western blot for MM-9 and tissue inhibitor of metalloproteinase-1 expression.
MMP-9 plasma levels were increased in patients affected by type A and type B aortic dissection presenting within 1 h from onset of symptoms compared to controls (29.3 +/- 16.1 and 16.7 +/- 2.1 ng/ml versus 7.74 +/- 1.6 ng/ml, P < 0.03, respectively). No differences were detected in MMP-2 plasma levels compared to controls (4.84 +/- 1.2 ng/ml for type A and 6.16 +/- 0.6 ng/ml versus 3.17 +/- 1.0 ng/ml for controls, P = NS, respectively). In type B aortic dissection, mean MMP-9 plasma levels increased significantly from hospital admission to 2-month follow-up (16.7 +/- 2.1 ng/ml versus 58.0 +/- 8.2 ng/ml, P < 0.0001). Conversely, no difference in MMP-2 plasma levels was evident during follow-up (6.16 +/- 0.6 ng/ml versus 4.28 +/- 0.4 ng/ml, P = NS, respectively). Low-moderate (+/++) expression of MMP-9 was evident at immunohistochemistry in the acute phase whereas a marked expression (++++) was detected in the subacute phase.
This pilot study suggests that the acute and subacute phase of both type A and type B aortic dissection is characterized by an increase of MMP-9 plasma levels. A marked increase is also evident in the subacute phase of medically treated type B aortic dissection as an expression of aortic wall remodelling. An increase of proteolytic activity could accompany attempts of the dissected aorta to heal itself but such a phenomena might further weaken the aortic wall, predisposing it to dilation and/or rupture.
主动脉夹层的特征是急性期的中层剥离和亚急性期至慢性期的血管壁修复。基质金属蛋白酶（MMPs）通过降解细胞外基质，可能在这些过程中起重要作用。MMPs水平升高可能为诊断急性或慢性主动脉病变提供契机。我们研究了MMP-9和MMP-2在主动脉夹层不同阶段的潜在诊断作用。
采用酶联免疫吸附测定技术评估1例急性主动脉夹层患者（9例A型，4例B型）的血浆MMPs水平。10名健康受试者作为对照。对于接受药物治疗的B型主动脉夹层患者，还评估了血浆曲线（症状发作后1、3、6、12、24、48和96小时；1和2周；以及2个月）。通过免疫组织化学和蛋白质印迹法评估手术中获取的主动脉组织样本中MMP-9和金属蛋白酶组织抑制剂-1的表达。
与对照组相比，症状发作后1小时内出现的A型和B型主动脉夹层患者的MMP-9血浆水平升高（分别为29.3±16.1和16.7±2.1 ng/ml，而对照组为7.74±1.6 ng/ml，P<0.03）。与对照组相比，MMP-2血浆水平未检测到差异（A型为4.84±1.2 ng/ml，B型为6.16±0.6 ng/ml，对照组为3.17±1.0 ng/ml，P=NS）。在B型主动脉夹层中，从入院到2个月随访期间，MMP-9平均血浆水平显著升高（16.7±2.1 ng/ml对58.0±8.2 ng/ml，P<0.0001）。相反，随访期间MMP-2血浆水平无明显差异（6.16±0.6 ng/ml对4.28±0.4 ng/ml，P=NS）。免疫组织化学显示急性期MMP-9呈低至中度（+/++）表达而亚急性期则检测到明显表达（++++）。
这项初步研究表明，A型和B型主动脉夹层的急性期和亚急性期的特征均为MMP-9血浆水平升高。在接受药物治疗的B型主动脉夹层亚急性期，MMP-9血浆水平也显著升高，这是主动脉壁重塑的表现。蛋白水解活性增加可能伴随剥离的主动脉自我修复的尝试，但这种现象可能会进一步削弱主动脉壁，使其易于扩张和/或破裂。
