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Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1268-73. Epub 2003 Jan 22.

PPARdelta is a very low-density lipoprotein sensor in macrophages.

Author information

1
The Salk Institute for Biological Studies, Howard Hughes Medical Institute, La Jolla, CA 90237, USA.

Abstract

Although triglyceride-rich particles, such as very low-density lipoprotein (VLDL), contribute significantly to human atherogenesis, the molecular basis for lipoprotein-driven pathogenicity is poorly understood. We demonstrate that in macrophages, VLDL functions as a transcriptional regulator via the activation of the nuclear receptor peroxisome proliferator-activated receptor delta. The signaling components of native VLDL are its triglycerides, whose activity is enhanced by lipoprotein lipase. Generation of peroxisome proliferator-activated receptor delta null macrophages verifies the absolute requirement of this transcription factor in mediating the VLDL response. Thus, our data reveal a pathway through which dietary triglycerides and VLDL can directly regulate gene expression in atherosclerotic lesions.

PMID:
12540828
PMCID:
PMC298762
DOI:
10.1073/pnas.0337331100
[Indexed for MEDLINE]
Free PMC Article

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