A wild-type mouse-based model for the regression of inflammation in atherosclerosis.
Atherosclerosis can be induced by the injection of a gain-of-function mutant of proprotein convertase subtilisin/kexin type 9 (PCSK9)-encoding adeno-associated viral vector (AAVmPCSK9), avoiding the need for knockout mice models, such as low-density lipoprotein receptor deficient mice. As regression...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5349694?pdf=render |
| _version_ | 1818137795746594816 |
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| author | Michael Peled Hitoo Nishi Ada Weinstock Tessa J Barrett Felix Zhou Alexandra Quezada Edward A Fisher |
| author_facet | Michael Peled Hitoo Nishi Ada Weinstock Tessa J Barrett Felix Zhou Alexandra Quezada Edward A Fisher |
| author_sort | Michael Peled |
| collection | DOAJ |
| description | Atherosclerosis can be induced by the injection of a gain-of-function mutant of proprotein convertase subtilisin/kexin type 9 (PCSK9)-encoding adeno-associated viral vector (AAVmPCSK9), avoiding the need for knockout mice models, such as low-density lipoprotein receptor deficient mice. As regression of atherosclerosis is a crucial therapeutic goal, we aimed to establish a regression model based on AAVmPCSK9, which will eliminate the need for germ-line genetic modifications. C57BL6/J mice were injected with AAVmPCSK9 and were fed with Western diet for 16 weeks, followed by reversal of hyperlipidemia by a diet switch to chow and treatment with a microsomal triglyceride transfer protein inhibitor (MTPi). Sixteen weeks following AAVmPCSK9 injection, mice had advanced atherosclerotic lesions in the aortic root. Surprisingly, diet switch to chow alone reversed hyperlipidemia to near normal levels, and the addition of MTPi completely normalized hyperlipidemia. A six week reversal of hyperlipidemia, either by diet switch alone or by diet switch and MTPi treatment, was accompanied by regression of atherosclerosis as defined by a significant decrease of macrophages in the atherosclerotic plaques, compared to baseline. Thus, we have established an atherosclerosis regression model that is independent of the genetic background. |
| first_indexed | 2024-12-11T10:01:59Z |
| format | Article |
| id | doaj.art-e22b88b89f024f4a956b9c97cb2c18fb |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T10:01:59Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-e22b88b89f024f4a956b9c97cb2c18fb2022-12-22T01:12:06ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01123e017397510.1371/journal.pone.0173975A wild-type mouse-based model for the regression of inflammation in atherosclerosis.Michael PeledHitoo NishiAda WeinstockTessa J BarrettFelix ZhouAlexandra QuezadaEdward A FisherAtherosclerosis can be induced by the injection of a gain-of-function mutant of proprotein convertase subtilisin/kexin type 9 (PCSK9)-encoding adeno-associated viral vector (AAVmPCSK9), avoiding the need for knockout mice models, such as low-density lipoprotein receptor deficient mice. As regression of atherosclerosis is a crucial therapeutic goal, we aimed to establish a regression model based on AAVmPCSK9, which will eliminate the need for germ-line genetic modifications. C57BL6/J mice were injected with AAVmPCSK9 and were fed with Western diet for 16 weeks, followed by reversal of hyperlipidemia by a diet switch to chow and treatment with a microsomal triglyceride transfer protein inhibitor (MTPi). Sixteen weeks following AAVmPCSK9 injection, mice had advanced atherosclerotic lesions in the aortic root. Surprisingly, diet switch to chow alone reversed hyperlipidemia to near normal levels, and the addition of MTPi completely normalized hyperlipidemia. A six week reversal of hyperlipidemia, either by diet switch alone or by diet switch and MTPi treatment, was accompanied by regression of atherosclerosis as defined by a significant decrease of macrophages in the atherosclerotic plaques, compared to baseline. Thus, we have established an atherosclerosis regression model that is independent of the genetic background.http://europepmc.org/articles/PMC5349694?pdf=render |
| spellingShingle | Michael Peled Hitoo Nishi Ada Weinstock Tessa J Barrett Felix Zhou Alexandra Quezada Edward A Fisher A wild-type mouse-based model for the regression of inflammation in atherosclerosis. PLoS ONE |
| title | A wild-type mouse-based model for the regression of inflammation in atherosclerosis. |
| title_full | A wild-type mouse-based model for the regression of inflammation in atherosclerosis. |
| title_fullStr | A wild-type mouse-based model for the regression of inflammation in atherosclerosis. |
| title_full_unstemmed | A wild-type mouse-based model for the regression of inflammation in atherosclerosis. |
| title_short | A wild-type mouse-based model for the regression of inflammation in atherosclerosis. |
| title_sort | wild type mouse based model for the regression of inflammation in atherosclerosis |
| url | http://europepmc.org/articles/PMC5349694?pdf=render |
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