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基质金属蛋白酶-12 在主动脉夹层中的表达。

Expression of matrix metalloproteinase-12 in aortic dissection.

机构信息

Laboratory of Molecular Cardiology, Department of Cardiology; The First Affiliated Hospital Of Kunming Medical University, Kunming, 650032, China.

出版信息

BMC Cardiovasc Disord. 2013 May 3;13:34. doi: 10.1186/1471-2261-13-34.

Abstract

BACKGROUND

Aortic 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.

METHODS

The 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.

RESULTS

MMP-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).

CONCLUSION

The 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.

摘要

背景

主动脉夹层(AD)是一种大血管的急性病变,具有危险的病理条件和高残疾率和高死亡率。AD 的发病机制仍存在争议。基质金属蛋白酶-12(MMP-12)参与了许多病理过程,如腹主动脉瘤、动脉粥样硬化、肺气肿和癌症。然而,这种弹性蛋白酶在 AD 中很少被评估。本研究旨在研究 MMP-12 在主动脉组织中的表达,以期更好地了解 AD 的可能机制。

方法

通过逆转录聚合酶链反应(RT-PCR)、Western 印迹、免疫组织化学、荧光共振能量转移(FRET)活性测定和酶联免疫吸附试验(ELISA),分别分析和比较了 MMP-12 在主动脉组织和血清样本中的蛋白表达水平。从 12 名急性 Stanford A 夹层主动脉置换术患者的升主动脉组织标本和 4 名接受冠状动脉旁路移植术的冠心病(CAD)患者中获得组织标本。同时,从 15 名急性 Stanford A 夹层患者和 10 名健康个体(对照组)中采集血清样本。

结果

MMP-12 活性可在 AD 和 CAD 组中检测到,但 AD 组的水平高于 CAD 组(P<0.05)。AD 和健康组的血清样本中均存在 MMP-12 蛋白水解,AD 组的活性水平明显高于健康组(P<0.05)。对于 AD 患者,血清中 MMP-12 的活性高于主动脉壁(P<0.05)。MMP-12 活性可被 MMP 抑制剂 v 抑制(P<0.05)。

结论

本研究直接证明 MMP-12 蛋白水解活性存在于主动脉夹层患者的主动脉组织和血液样本中。MMP-12 可能作为一种有潜在临床诊断价值的工具和治疗靶点,用于血管损伤和修复。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1d2/3660235/9bf1f6bc50f9/1471-2261-13-34-1.jpg

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