Peroxisome proliferator-activated receptors

Abstract

An exciting and rapidly evolving area in vascular biology and atherosclerosis research over the past 3 years has been the establishment of peroxisome proliferator-activated receptor (PPAR) expression in the vascular and inflammatory cells, and the emerging picture of the roles these ligand-activated nuclear receptor/transcription factors might play in vascular biology and atherosclerosis. Such work is all the more compelling given the ongoing clinical use of PPAR activators in patients. Thiazolidinediones (PPAR-g agonists) are used as insulin sensitizers in diabetic patients known to be at extraordinarily high risk for cardiovascular disease, whereas fibrates (PPAR-a agonists) are used to treat dyslipidemia, particularly in the case of high triglycerides and low high-density lipoprotein cholesterol.

Regression of pre-established atherosclerosis in the apoE−/− mouse by conjugated linoleic acid

“…The insulin-sensitizing thiazolidinedione drugs also bind with high affinity to PPARγ [46]. When activated by its ligands, PPARγ heterodimerizes with the retinoid X receptor (RXR) and binds to specific peroxisomeproliferator-response elements (PPREs) located in the promoter of target genes [47][48][49], inducing expression of the target gene.…”

Agoniści receptorów aktywowanych proliferatorami eroksysomów w farmakoterapii. Obecne znaczenie i perspektywy zastosowania

“…Stąd do powszechnego użycia weszła nazwa "receptorów aktywowanych proliferatorami peroksysomów" (ang. peroxisome proliferators-activated receptors, PPAR), choć zaznaczyć należy, iż w ludzkich komórkach, w przeciwieństwie do badań doświadczalnych, agoniści PPAR nie powodują proliferacji peroksysomów, lecz jedynie nasilenie ich aktywności [6]. Nazwa PPAR ma zatem znaczenie historyczne.…”

“…PPAR-α są zlokalizowane przede wszystkim w wątrobie, sercu lub nerkach, a aktywacja tego podtypu receptora jest związana z mitochondrialną i pe-roksysomalną regulacją przemian lipidów (transport i przemiany kwasów tłusz-czowych, β-oksydacja, synteza ciał ketonowych) [6][7][8].…”

Peroxisome proliferator-activated receptors as therapeutic targets in inflammation**Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.

“…In vivo studies support this possibility. Several PPAR-␥ agonists have been shown to limit atherosclerosis in various mouse models of atherosclerosis (12). Moreover, clinical data in humans on surrogate end points of atherosclerosis also are suggestive of potential TZD benefits.…”

“…Alternatively, if PPARs were expressed in vascular and inflammatory cells, then PPAR activation could have direct effects on atherosclerosis by inducing or repressing specific relevant target genes (10). In fact, extensive data from many groups now establish PPAR-␣, -␥, and -␦ expression throughout the vasculature and in many inflammatory cells, as well as an ever-expanding list of PPAR target genes involved in vascular biology (11,12). Most, but not all, of these data suggests activation of PPAR-␥ and -␣, the isoforms targeted by synthetic agonists in current clinical use, would decrease atherosclerosis and/or inflammation.…”