Title
Human CETP aggravates atherosclerosis by increasing VLDL-cholesterol rather than by decreasing HDL-cholesterol in APOE*3-Leiden mice
Author
de Vries-van der Weij, J.
Zadelaar, A.S.M.
Toet, K.
Havekes, L.M.
Kooistra, T.
Rensen, P.C.N.
TNO Kwaliteit van Leven
Publication year
2009
Abstract
Objective: Cholesteryl ester transfer protein (CETP) adversely affects the plasma lipoprotein profile by increasing VLDL-cholesterol and decreasing HDL-cholesterol. The relative contribution of either of these changes to atherosclerosis development is not known. We investigated to what extent the increase in VLDL-cholesterol can explain the atherogenic action of human CETP expression in APOE*3-Leiden (E3L) mice, a model for human-like lipoprotein metabolism. Methods and results: E3L mice and E3L.CETP mice were fed a low cholesterol (LC) diet, resulting in a 4-fold increased VLDL-cholesterol level as well as a 9-fold increased atherosclerotic lesion area in the aortic root in E3L.CETP mice compared to E3L-LC mice. E3L mice fed a high cholesterol (HC) diet to match the increased VLDL-cholesterol levels in E3L.CETP mice, displayed a similar atherosclerotic lesion area as observed in E3L.CETP mice. Hence, the CETP-induced raise in atherosclerosis can largely be explained by increased VLDL-cholesterol. Despite similar atherosclerosis development, E3L.CETP mice had lower HDL-cholesterol as compared to E3L-HC mice (-49%) indicating that the HDL-cholesterol lowering effect of CETP is unlikely to contribute to atherosclerosis development in this experimental setting. Remarkably, atherosclerotic lesions in CETP-expressing mice were enriched in collagen, suggesting a role of CETP or the diet in modifying lesion collagen content. Conclusions: In this experimental setting, the proatherogenic effect of CETP is largely explained by increased VLDL-cholesterol. © 2009 Elsevier Ireland Ltd. All rights reserved.
Subject
Biology
Biomedical Research
Atherosclerosis
Cholesteryl ester transfer protein
Lesion stability
Lipoproteins
To reference this document use:
http://resolver.tudelft.nl/uuid:15a8197e-ab0f-4346-bf27-cc3f07004521
DOI
https://doi.org/10.1016/j.atherosclerosis.2009.02.038
TNO identifier
241717
ISSN
0021-9150
Source
Atherosclerosis, 206 (1), 153-158
Document type
article