PPARs and Their Emerging Role in Vascular Biology …

AbstractFor many years, advances in understanding steroid hormone action typically proceeded through sequential stages that involved first identifying the role of a putative hormone, then isolating it, often from large quantities of body fluid, and ultimately identifying the nuclear receptor through which the cellular effects were being achieved (1). More recently, this stepwise progression has been reversed by modern molecular biology techniques allowing rapid identification of many genes as encoding nuclear receptors based on structural motifs even without any information regarding the functional role of these so called orphan receptors. This process has been termed reverse endocrinology (1). Peroxisome proliferator-activated receptors (PPARs) were examples of such orphan receptors, although their status changed through the serendipitous discovery of synthetic ligands that could bind to PPARs (2). The fact that these synthetic agonists are now in clinical use for treating diabetes mellitus (DM) and dyslipidemia has helped draw attention to this nuclear receptor subfamily and its potential as a therapeutic target (3). The identification of a possible role for PPARs in inflammation and atherosclerosis has only heightened this interest (4).

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PPARs and Their Emerging Role in Vascular Biology ...