Cigarette smoke enhances abdominal aortic aneurysm formation in angiotensin II-treated apolipoprotein E-deficient mice
Autor: | Stefan Lebrun, Michael Lietz, Katrin Stolle, Thomas Wallerath, An Berges |
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Rok vydání: | 2010 |
Předmět: |
Male
Apolipoprotein E medicine.medical_specialty Apolipoprotein B Blood Pressure Peptide hormone Toxicology Mice Aortic aneurysm Apolipoproteins E Smoke Internal medicine Tobacco Renin–angiotensin system Hyperlipidemia medicine Animals Sidestream smoke biology Chemistry Angiotensin II Body Weight Tissue Inhibitor of Metalloproteinases General Medicine medicine.disease Matrix Metalloproteinases Disease Models Animal Endocrinology cardiovascular system biology.protein Aortic Aneurysm Abdominal |
Zdroj: | Toxicology Letters. 199:403-409 |
ISSN: | 0378-4274 |
DOI: | 10.1016/j.toxlet.2010.10.005 |
Popis: | Cigarette smoke, hyperlipidemia, and hypertension with the risk of development and progression of atherosclerosis and associated pathologies such as abdominal aortic aneurysm (AAA) are correlated. We examined the interaction of cigarette mainstream smoke (MS) and angiotensin-II (Ang II)-induced hypertension in the atherosclerotic process using hyperlipidemic apolipoprotein E-knockout (ApoE(-/-)) mice. ApoE(-/-) mice were treated with Ang II for 4 weeks and then further exposed to MS or to fresh air for 4 weeks. AAA formation was observed in all mice treated with Ang II, regardless of smoke exposure; however, smoke exposure increased the incidence of AAA in these mice. Ang II treatment resulted in higher gene expression of matrix metalloproteinases (MMP)-2, -3, -8, -9, and -12 in the abdominal aortas, which was further increased by MS exposure. The proteolytic activity of MMP-2 and MMP-9 was also enhanced in Ang II-treated mice exposed to MS, but only minor changes were seen with either smoke exposure or Ang II treatment alone. This study shows for the first time that both formation and severity of AAA in hypertensive ApoE(-/-) mice are accelerated by exposure to MS and that the proteolytic activity of MMPs is enhanced by the combination of Ang II and MS. |
Databáze: | OpenAIRE |
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