Expression of matrix metalloproteinase-12 in aortic dissection

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.

MMP-12 and Macrophage Activation in Acute Aortic Dissection

“…Among the MMPs, we identified MMP-12, which is exclusively released by macrophages, as a specific marker for Stanford-A AAD [2,8]. Further confirming our results, the expression of MMP-12 has been reported within aortic specimens [9,10] both in humans and in mice [11], and it has been specifically related to the pathogenesis of aneurysms occurring both in ascending and in abdominal aortas [12,13]. This is different from what occurs with MMP-2 and MMP-9, which are released by several immune cells and have been related to matrix remodeling also in atherosclerotic plaque [14,15,16,17].…”

Variants of genes encoding collagens and matrix metalloproteinase system increased the risk of aortic dissection

“…The LOF variants in these genes may break the inner connection of ECM, thereupon interrupt the homeostasis of ECM. The MMPs/TIMPs have robust associations with AD in association studies (Song et al, 2013;Wang et al, 2014;Zhang et al, 2009), indicating that functional variants within MMPs/TIMPs genes may lead to degrading of various components of the aortic ECM or result in aorta inflammation, therefore, playing an important role in AD pathogenesis (Theruvath et al, 2012). However, none of the MMPs coding genes have been regarded as AD-causing gene in the past.…”

Knockdown of MMP12 inhibits the growth and invasion of lung adenocarcinoma cells

“…4 MMP-12 is expressed in aortic dissection patients as a clinically diagnostic tool for vascular injury, 5 and regulates adipose tissue expansion, insulin sensitivity, and expression of inducible nitric oxide synthase. 6 MMP12 is overexpressed in cervical scrape cells from cervical precursor lesions, 7 and contributes to the pathogenesis of cervical cancer.…”