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Review
. 2015:2015:271983.
doi: 10.1155/2015/271983. Epub 2015 Oct 26.

Peroxisome Proliferator-Activated Receptors and the Heart: Lessons from the Past and Future Directions

Wang-Soo Lee  1 , Jaetaek Kim  2
Affiliations
Review

Peroxisome Proliferator-Activated Receptors and the Heart: Lessons from the Past and Future Directions

Wang-Soo Lee et al. PPAR Res. 2015.

Abstract

Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear family of ligand activated transcriptional factors and comprise three different isoforms, PPAR-α, PPAR-β/δ, and PPAR-γ. The main role of PPARs is to regulate the expression of genes involved in lipid and glucose metabolism. Several studies have demonstrated that PPAR agonists improve dyslipidemia and glucose control in animals, supporting their potential as a promising therapeutic option to treat diabetes and dyslipidemia. However, substantial differences exist in the therapeutic or adverse effects of specific drug candidates, and clinical studies have yielded inconsistent data on their cardioprotective effects. This review summarizes the current knowledge regarding the molecular function of PPARs and the mechanisms of the PPAR regulation by posttranslational modification in the heart. We also describe the results and lessons learned from important clinical trials on PPAR agonists and discuss the potential future directions for this class of drugs.

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Figures

Figure 1
Figure 1
Structure of PPAR and its transactivation or transrepression process. In the absence of ligand, the PPAR-RXR heterodimer recruits corepressors (left process). When ligand binds, conformational changes in PPAR-RXR induce dissociation of corepressor complex. Active transcriptional complex assembles with coactivator proteins. PPAR binds to PPRE and assembles coactivator complexes (right process). PGC-1α: PPAR-γ coactivator 1α, NCoR: nuclear receptor corepressor, SMART: silencing mediator of retinoid and thyroid hormone receptor, AF: activation function, DBD: DNA-binding domain, HD: hinge domain, LBD: ligand-binding domain, RXR: retinoid X receptor, and PPRE: peroxisome proliferator response element.
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References

    1. Oyekan A. PPARs and their effects on the cardiovascular system. Clinical and Experimental Hypertension. 2011;33(5):287–293. doi: 10.3109/10641963.2010.531845. - DOI - PubMed
    1. Chen R., Liang F., Moriya J., et al. Peroxisome proliferator-activated receptors (PPARs) and their agonists for hypertension and heart failure: are the reagents beneficial or harmful? International Journal of Cardiology. 2008;130(2):131–139. doi: 10.1016/j.ijcard.2008.03.080. - DOI - PubMed
    1. Desvergne B., Wahli W. Peroxisome proliferator activated receptors: nuclear control of metabolism. Endocrine Reviews. 1999;20(5):649–688. - PubMed
    1. Michalik L., Auwerx J., Berger J. P., et al. International union of pharmacology. LXI. Peroxisome proliferator-activated receptors. Pharmacological Reviews. 2006;58(4):726–741. doi: 10.1124/pr.58.4.5. - DOI - PubMed
    1. Bookout A. L., Jeong Y., Downes M., Yu R. T., Evans R. M., Mangelsdorf D. J. Anatomical profiling of nuclear receptor expression reveals a hierarchical transcriptional network. Cell. 2006;126(4):789–799. doi: 10.1016/j.cell.2006.06.049. - DOI - PMC - PubMed

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