Elastase activity: The role of elastase in aortic aneurysm formation

Busuttil, Ronald W.; Rinderbriecht, Heinrich; Flesher, Ann; Carmack, C

doi:10.1016/0022-4804(82)90093-2

Cited by 159 publications

(52 citation statements)

References 5 publications

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“…Aneurysm expansion is an active process and involves inflammation, proteolysis, and protein deposition. 3,[17][18][19] The MMP family of enzymes has been implicated in this degradation of the aortic wall. 20, 21 The MMPs are also intimately involved with development and rupture of atherosclerotic plaques.…”

Section: Discussionmentioning

confidence: 99%

Stromelysin-1 (Matrix Metalloproteinase-3) and Tissue Inhibitor of Metalloproteinase-3 Are Overexpressed in the Wall of Abdominal Aortic Aneurysms

et al. 2002

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Background-Atherosclerosis is implicated in the pathogenesis of abdominal aortic aneurysm (AAA) but more often causes aortic occlusive disease (AOD). The matrix metalloproteinases (MMPs) degrade extracellular matrix and may play a central role in the pathogenesis of AAA. The aim of this study was to examine differences in the patterns of MMP and MMP inhibitor expression between AAA and AOD. Methods and Results-The expression of mRNA for 14 MMPs and 4 tissue inhibitors of metalloproteinases (TIMPs) was estimated in samples of aortic wall from 8 patients with AAA and 8 with AOD using the reverse-transcriptase polymerase chain reaction with a synthetic multicompetitor standard. AAA wall expressed significantly more stromelysin-1 (MMP-3) (mean log 10 ratio [copy enzyme cDNA/copy GAPDH cDNA], Ϫ1.9; range, Ϫ3.3 to Ϫ0.7) than the AOD wall (mean, 4; range, Ϫ5.7 to Ϫ2.4), PϽ0.005. TIMP-3 expression was significantly higher in AAA (mean, Ϫ1.7; range, Ϫ2.9 to Ϫ1.0) than AOD (mean, Ϫ3.6; range, Ϫ5.7 to Ϫ1.8), PϽ0.01. Expression of 8 other MMPs (1, 2, 7, 9, 11, 12, 14, and 17) was detected and was similar in AAA and AOD. Expression of the remaining 5 MMPs (Ϫ8, Ϫ10, Ϫ13, Ϫ15, and Ϫ16) was not detected in any of the samples. Conclusions-Both AAA and AOD walls express similar levels of a wide range of MMPs, including cell membranebound MT-MMPs. Stromelysin-1 (MMP-3) and TIMP-3 were, however, over expressed in the AAA samples and may be involved aneurysm pathogenesis. Stromelysin-1 could provide a target for pharmacological inhibition.

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Section: Discussionmentioning

confidence: 99%

Stromelysin-1 (Matrix Metalloproteinase-3) and Tissue Inhibitor of Metalloproteinase-3 Are Overexpressed in the Wall of Abdominal Aortic Aneurysms

et al. 2002

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“…The elastase-induced AAA model is very popular and is considered to be suitable for analysis of the mechanisms of the pathogenesis of AAA, because several previous reports showed that elastase activity plays an important role in the progression of AAA. 14,15 In addition, using chimeric decoy oligodeoxynucleotide (ODN) against NFB and ets, we demonstrated successful treatment of experimental AAA in a rat hypertension model, with the anticipation of developing future therapy.…”

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confidence: 99%

Hypertension Accelerated Experimental Abdominal Aortic Aneurysm Through Upregulation of Nuclear Factor κB and Ets

et al. 2006

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Abstract-In this study, we focused on the effect of hypertension on the transcription factors nuclear factor B (NFB) and ets in the mechanisms of abdominal aortic aneurysm (AAA), and we investigated how hypertension affects the progression of AAA. AAA was produced by elastase perfusion in hypertensive rats and normotensive rats. The size of AAA rapidly increased in hypertensive rats as compared with normotensive rats. Western blot analysis demonstrated that the expression of matrix metalloproteinase (MMP)-2, -3 , -9, and -12, as well as intercellular adhesion molecule, was increased in hypertensive AAA rats, accompanied by upregulation of NFB and ets. Moreover, in situ zymography showed that the activity of MMPs was increased in the aorta of a hypertensive AAA model as compared with that in a normotensive AAA model. Interestingly, transfection of chimeric decoy oligodeoxynucleotide (ODN) resulted in significant inhibition of aortic dilatation both in normotensive and hypertensive rats at 4 weeks after transfection. Destruction of elastic fibers was also significantly inhibited by transfection of chimeric decoy ODN in both hypertensive rats and normotensive rats. The expression of MMP-2, -3, -9, and -12, as well as intercellular adhesion molecule, was significantly attenuated by the chimeric decoy ODN, accompanied by inhibition of the migration of macrophages. Also, the effect of chimeric decoy ODN was confirmed in an organ culture. The present study demonstrated that hypertension accelerated the progression of experimental AAA through upregulation of NFB and ets. Inhibition of NFB and ets could be a novel therapeutic strategy to treat AAA in hypertensive patients. bdominal aortic aneurysm (AAA) is a common degenerative condition associated with aging and atherosclerosis. 1 Because the main pathogenesis of AAA is considered to be based on atherosclerosis, patients with aneurysms and atherosclerotic disease share similar risk factors, including male sex, 2 older age, 3 and a lipid profile that includes lower high-density lipoprotein and higher triglyceride and lowdensity lipoprotein concentrations. 4 However, the risk factors for atherosclerosis and AAA are not completely the same, because there are certain pathogenetic, epidemiological, and genetic differences between these 2 diseases. 5,6 Indeed, although hypertension induces sheer stress, oxidative stress, and vascular inflammation followed by atherosclerosis, a consistent relation between blood pressure and the prevalence of AAA has not been demonstrated. 7,8 Hypertension has been reported to be both independently associated with AAA and not associated with AAA. 8,9 Basic phenomena in the pathogenesis of AAA are degradation of extracellular matrix components and loss of structural integrity of the aortic wall. 10 AAA disease typically involves tissue inflammation as seen by the presence of inflammatory cells, which are considered to participate in the immunopathogenesis of AAA leading to destruction of the aortic matrix. 11,12 Recent investigations have emph...

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“…7 " 9 More recently, two reports have suggested that the ratios of elastase-like activity to a-1-antiproteinase activity is increased in aortic tissue taken from patients with ruptured AAAs compared with similar tissues taken from patients with atherosclerotic occlusive disease. 1011 However, these studies failed to identify the enzyme species responsible for the proteolytic activity, the origin, or the location of these activities within the vessel wall.…”

mentioning

confidence: 99%

Connective tissue proteinases and inhibitors in abdominal aortic aneurysms. Involvement of the vasa vasorum in the pathogenesis of aortic aneurysms.

Herron

Unemori

Wong

et al. 1991

Arterioscler Thromb

145

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T he development of irreversible dilations of the infrarenal aorta has been attributed to hemodynamic disturbances as well as to structural and metabolic changes within the vessel wall. 1 -2 Chemical and histological analyses have demonstrated significant decreases in the two major structural proteins, collagen and elastin, in dilated vascular tissue from patients undergoing corrective surgery for abdominal aortic aneurysm (AAA) disease. 34 Experimentally, it has been shown that circumferential arterial wall stress is borne primarily by elastin and that collagen maintains the integrity of the arterial wall, as enzymatic hydrolysis of collagen results in vessel rupture, whereas degradation of

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Elastase activity: The role of elastase in aortic aneurysm formation

Cited by 159 publications

References 5 publications

Stromelysin-1 (Matrix Metalloproteinase-3) and Tissue Inhibitor of Metalloproteinase-3 Are Overexpressed in the Wall of Abdominal Aortic Aneurysms

Stromelysin-1 (Matrix Metalloproteinase-3) and Tissue Inhibitor of Metalloproteinase-3 Are Overexpressed in the Wall of Abdominal Aortic Aneurysms

Hypertension Accelerated Experimental Abdominal Aortic Aneurysm Through Upregulation of Nuclear Factor κB and Ets

Connective tissue proteinases and inhibitors in abdominal aortic aneurysms. Involvement of the vasa vasorum in the pathogenesis of aortic aneurysms.

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