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Plasma cholesterol lowering in an AngII-infused atherosclerotic mouse model with moderate hypercholesterolemia
Karolinska Inst, Sweden.
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
Uppsala Univ, Sweden.
Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.ORCID iD: 0000-0002-9095-403X
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2018 (English)In: International Journal of Molecular Medicine, ISSN 1107-3756, E-ISSN 1791-244X, Vol. 42, no 1, p. 471-478Article in journal (Refereed) Published
Abstract [en]

Atherosclerosis is the main underlying causes of cardiovascular disease. There is a well-established association between high blood cholesterol levels and the extent of atherosclerosis. Furthermore, atherosclerosis has been proposed to augment abdominal aortic aneurysm (AAA) formation. As patients with AAA often have parallel atherosclerotic disease and are therefore often on cholesterol-lowering therapy, it is not possible to fully address the independent effects of plasma cholesterol lowering (PCL) treatment on AAA. The present study investigated the effect of angiotensin II (AngII)-infusion in modestly hypercholesterolemic Ldlr(-/-)Apob(100/100)Mttp(flox/flox)Mx1-Cre mice with or without PCL treatment on a morphological and molecular level, in terms of atherosclerosis and AAA development. AngII infusion in the study mice resulted in an increased atherosclerotic lesion area and increased infiltration of inflammatory leukocytes, which was not observed in mice with PCL induced prior to AngII infusion. This suggested that AngII infusion in this mouse model induced atherosclerosis development, and that plasma cholesterol levels represent a controlling factor. Furthermore, AngII infusion in Ldlr(-/-)Apob(100/100)Mttp(flox/flox)Mx1-Cre mice caused a modest aneurysmal phenotype, and no differences in AAA development were observed between the different study groups. However, the fact that modest hypercholesterolemic mice did not develop AAA in a classical aneurysmal model indicated that plasma cholesterol levels are important for disease development.

Place, publisher, year, edition, pages
SPANDIDOS PUBL LTD , 2018. Vol. 42, no 1, p. 471-478
Keywords [en]
abdominal aortic aneurysm; cholesterol; angiotensin II; smooth muscle cell
National Category
Cardiac and Cardiovascular Systems
Identifiers
URN: urn:nbn:se:liu:diva-150277DOI: 10.3892/ijmm.2018.3619ISI: 000440580900046PubMedID: 29658561OAI: oai:DiVA.org:liu-150277DiVA, id: diva2:1239705
Available from: 2018-08-17 Created: 2018-08-17 Last updated: 2018-08-17

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Vorkapic, EminaLänne, TosteWågsäter, Dick
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Division of Drug ResearchFaculty of Medicine and Health SciencesDivision of Cardiovascular MedicineDepartment of Thoracic and Vascular Surgery
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International Journal of Molecular Medicine
Cardiac and Cardiovascular Systems

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