[Hyperlipidemia and peroxisome proliferator-activated receptor (PPAR)--regulation of the PPARalpha gene by CLOCK: BMAL1].
The main pathological findings in atherosclerosis include abnormal reactions of neutrophils, lymphocytes and monocytes/macrophages, vascular smooth muscle cells and vascular endothelial cells, and the accumulation of cholesterol ester in the arterial wall. Therefore, investigating the effects of these abnormal reactions on the arterial wall may improve understanding of the mechanisms underlying atherosclerosis. Three types of peroxisome proliferator-activated receptors (PPARs): PPARalpha, PPARbeta/delta, and PPARgamma are expressed in endothelial cells. In endothelial cells, the ligands/activators for PPARalpha and PPARgamma increase Cu2+, Zn2+ -superoxide dismutase. In addition, the phorbol myristate acetate (PMA)-stimulated 22 kDa-subunit (p22phox) protein levels and 47 kDa-subunit (p47phox) protein levels in NADPH (superoxide generating enzyme nicotinamide adenine dinucleotide phosphate (reduced form)) oxidase were decreased by treatment with PPARalpha and PPARgamma ligands/activators. Recently, we showed that the CLOCK: BMAL1 heterodimer regulates the PPARalpha gene via promoter of PPARalpha. Moreover, we report a patient with severe hypertriglyceridemia associated with anemia and hypoalbuminemia, in which the former may have caused the latter two conditions. This is the first reported case of abrupt onset of severe hypertriglyceridemia resulting in suppression of bone marrow and liver function. Here, based on recent studies including our own, we describe the relationships between risk factors for atherosclerosis, especially hyperlipidemia and PPARs and the molecular mechanisms that govern lipid metabolism in the arteries.
Inoue
Ikuo
I
Fourth Department of Medicine, Saitama Medical School.
D056930:ARNTL Transcription Factors; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D004734:Energy Metabolism / Q000502:physiology; D006949:Hyperlipidemias / Q000209:etiology*; D008024:Ligands; D010088:Oxidoreductases / Q000502:physiology; D047492:Peroxisome Proliferator-Activated Receptors / Q000502:physiology*; D020675:Peroxisomes / Q000378:metabolism; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology*
D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D008024:Ligands; D010088:Oxidoreductases; D047492:Peroxisome Proliferator-Activated Receptors; D015534:Trans-Activators; D014157:Transcription Factors