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(Circulation Research. 2004;95:1137.)
© 2004 American Heart Association, Inc.

Editorials

Oxidative Stress and Peroxisome Proliferator–Activated Receptors

Reversing the Curse?

Pallavi R. Devchand, Ouliana Ziouzenkova, Jorge Plutzky

From the Donald W. Reynolds Cardiovascular Clinical Research Center, Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass.

Correspondence to Dr Jorge Plutzky, Brigham and Women’s Hospital, 77 Ave Louis Pasteur, NRB740, Boston, MA 02115. E-mail jplutzky@rics.bwh.harvard.edu

See related article, pages 1174–1182

Key Words: PPARs • oxidation • LDL • NADPH • inflammation

An extract of the first 250 words of the full text is provided, because this article has no abstract.

The most common view of lipoproteins focuses on their role in lipid transport.¹ By making lipids miscible in plasma, lipoproteins deliver triglycerides, and their incorporated fatty acids, to muscle for energy use or to adipose tissue for storage, the latter seeming all too often the case. Likewise, lipoprotein transport provides cholesterol to cells for essential functions like membrane formation and steroid hormone synthesis. More recent work has expanded this perspective, revealing how lipoproteins can help deliver specific signals to the nucleus of cells, inducing targeted transcriptional responses in tissues far removed from where the lipoprotein particle originated. Indeed, extensive data now identify lipid signaling to the nucleus in many key biological pathways, including cellular determination, cell differentiation, and adaptive homeostasis.²

One process in which lipoproteins and bioactive lipid metabolites have been strongly implicated is inflammation, including both its initiation and resolution.² In this regard, peroxisome proliferator–activated receptors, or PPARs, have received considerable attention as a mechanism for transducing such lipid signals into transcriptional responses.³ PPARs, members of the steroid hormone receptor family, help regulate the expression of key genes involved in lipid metabolism, adipogenesis, and glucose control; more recent evidence suggests a role for PPARs in inflammation and atherosclerosis as well.⁴ The three PPAR isoforms (PPAR-, PPAR-ß, PPAR-) share many attributes while maintaining distinct features, including differences in expression patterns, cognate ligands, coactivator/corepressor interactions, target genes, and species differences, with the latter including peroxisomal proliferation itself.⁵ Despite this daunting complexity, the ongoing clinical use of synthetic PPAR agonists . . . [Full Text of this Article]

Related Article:

Peroxisome Proliferator–Activated Receptor Induces NADPH Oxidase Activity in Macrophages, Leading to the Generation of LDL with PPAR- Activation Properties

Elisabeth Teissier, Atsushi Nohara, Giulia Chinetti, Réjane Paumelle, Bertrand Cariou, Jean-Charles Fruchart, Ralf P. Brandes, Ajay Shah, and Bart Staels
Circ. Res. 2004 95: 1174-1182. [Abstract] [Full Text] [PDF]

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