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- Title
CETP Expression in Bone-Marrow-Derived Cells Reduces the Inflammatory Features of Atherosclerosis in Hypercholesterolemic Mice.
- Authors
Rentz, Thiago; Dorighello, Gabriel G.; dos Santos, Renata R.; Barreto, Lohanna M.; Freitas, Israelle N.; Lazaro, Carolina M.; Razolli, Daniela S.; Cazita, Patricia M.; Oliveira, Helena C. F.
- Abstract
CETP activity reduces plasma HDL-cholesterol concentrations, a correlate of an increased risk of atherosclerotic events. However, our recent findings suggest that CETP expression in macrophages promotes an intracellular antioxidant state, reduces free cholesterol accumulation and phagocytosis, and attenuates pro-inflammatory gene expression. To determine whether CETP expression in macrophages affects atherosclerosis development, we transplanted bone marrow from transgenic mice expressing simian CETP or non-expressing littermates into hypercholesterolemic LDL-receptor-deficient mice. The CETP expression did not change the lipid-stained lesion areas but decreased the macrophage content (CD68), neutrophil accumulation (LY6G), and TNF-α aorta content of young male transplanted mice and decreased LY6G, TNF-α, iNOS, and nitrotyrosine (3-NT) in aged female transplanted mice. These findings suggest that CETP expression in bone-marrow-derived cells reduces the inflammatory features of atherosclerosis. These novel mechanistic observations may help to explain the failure of CETP inhibitors in reducing atherosclerotic events in humans.
- Subjects
GENE expression; TRANSGENIC mice; BONE marrow; MICE; ATHEROSCLEROSIS; LOW density lipoprotein receptors
- Publication
Biomolecules (2218-273X), 2023, Vol 13, Issue 10, p1556
- ISSN
2218-273X
- Publication type
Article
- DOI
10.3390/biom13101556