Abstract
BackgroundAortic dissection(AD) is an acute process of large blood vessels characterized by dangerous pathogenic conditions and high disability and high mortality. The pathogenesis of AD remains debated. Matrix metalloproteinase-12 (MMP-12) participates in many pathological processes such as abdominal aortic aneurysm, atherosclerosis, emphysema and cancer. However, this elastase has rarely been assessed in the presence of AD. The aim of the present study was to investigate the expression of MMP-12 in aortic tissue so as to offer a better understanding of the possible mechanisms of AD.MethodsThe protein expression levels of MMP-12 were analyzed and compared in aorta tissue and the blood serum samples by reverse transcription polymerase chain reaction(RT-PCR), Western blotting, immuno-histochemistry, fluorescence resonance energy transfer ( FRET ) activity assay and enzyme-linked immuno sorbent assay ( ELISA ), respectively. Ascending aorta tissue specimens were obtained from 12 patients with an acute Stanford A-dissection at the time of aortic replacement, and from 4 patients with coronary artery disease (CAD) undergoing coronary artery bypass surgery. Meanwhile, serum samples were harvested from 15 patients with an acute Stanford A-dissection and 10 healthy individuals who served as the control group.ResultsMMP-12 activity could be detected in both AD and CAD groups, but the level in the AD group was higher than those in the CAD group (P < 0.05). MMP-12 proteolysis existed in both serum samples of the AD and healthy groups, and the activity level in the AD group was clearly higher than in the healthy group (P < 0.05). For AD patients, MMP-12 activity in serum was higher than in the aorta wall (P < 0.05). MMP-12 activity in the aortic wall tissue can be inhibited by MMP inhibitor v (P < 0.05).ConclusionThe present study directly demonstrates that MMP-12 proteolytic activity exists within the aorta specimens and blood samples from aortic dissection patients. MMP-12 might be of potential relevance as a clinically diagnostic tool and therapeutic target in vascular injury and repair.
Highlights
Aortic dissection(AD) is an acute process of large blood vessels characterized by dangerous pathogenic conditions and high disability and high mortality
The former researchers [13] showed that the expression of Matrix metalloproteinases (MMPs)-2 and Tissue inhibitors of matrix metalloproteinases (TIMPs)-2 in aortic samples from patients with acute aortic dissection were significantly lower than in aortic samples from patients undergoing coronary artery bypass, implied that an imbalance between TIMP-2/ MMP-2 and TIMP-2/MMP-9 might play an important role in the onset of aortic dissection
A possible explanation is that our gene expression studies considered the entry site of the dissection and not the whole aortic wall . we detected Matrix metalloproteinase-12 (MMP-12) mRNA in ascending aorta specimen obtained from patients operated on for coronary artery bypass surgery
Summary
Aortic dissection(AD) is an acute process of large blood vessels characterized by dangerous pathogenic conditions and high disability and high mortality. Matrix metalloproteinase-12 (MMP-12) participates in many pathological processes such as abdominal aortic aneurysm, atherosclerosis, emphysema and cancer. This elastase has rarely been assessed in the presence of AD. In the United States, aortic dissection and aneurysms rank among the 15 leading studies have focused on the role of MMPs in AD. Several investigators, applying both immunohistochemical techniques and zymography on acute dissection specimens, have reported increased MMP-9 and −2 expression at the site of the initial tear in patients with aortic dissection [7,8]. The former researchers [13] showed that the expression of MMP-2 and TIMP-2 in aortic samples from patients with acute aortic dissection were significantly lower than in aortic samples from patients undergoing coronary artery bypass, implied that an imbalance between TIMP-2/ MMP-2 and TIMP-2/MMP-9 might play an important role in the onset of aortic dissection
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