Plasma cholesterol lowering in an AngII‑infused atherosclerotic mouse model with moderate hypercholesterolemia

Rossignoli,Aránzazu; Vorkapic,Emina; Wanhainen,Anders; Länne,Toste; Skogberg,Josefin; Folestad,Erika; Wågsäter,Dick

doi:10.3892/ijmm.2018.3619

Plasma cholesterol lowering in an AngII‑infused atherosclerotic mouse model with moderate hypercholesterolemia

Authors:
- Aránzazu Rossignoli
- Emina Vorkapic
- Anders Wanhainen
- Toste Länne
- Josefin Skogberg
- Erika Folestad
- Dick Wågsäter
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Affiliations: Division of Vascular Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177 Stockholm, Sweden, Division of Drug Research, Department of Medical and Health Sciences, Linköping University, 58183 Linköping, Sweden, Department of Surgical Sciences, Section of Vascular Surgery, Uppsala University, 75185 Uppsala, Sweden, Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Linköping University, 58183 Linköping, Sweden
Published online on: April 5, 2018 https://doi.org/10.3892/ijmm.2018.3619
Pages: 471-478

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Abstract

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‑/‑Apob100/100Mttpflox/floxMx1‑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‑/‑Apob100/100Mttpflox/floxMx1‑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.

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