Endothelial Progenitor Cells and Angiogenesis Join the PPARty

F. Biscetti, R. Pola
2008 Circulation Research  
P eroxisome proliferator-activated receptors (PPARs) are ligand-inducible transcription factors that belong to the nuclear hormone receptor superfamily. 1 In mammals, the PPAR family consists of 3 subtypes of proteins encoded by separate genes: PPAR␣ (NR1C1), PPAR␥ (NR1C3), and PPAR␦ (also known as ␤ or NR1C2). 2 They act as heterodimers with the retinoid X receptor and regulate gene transcription by binding to specific response elements in the promoter of the target genes. 3 The classical
more » ... The classical biological activity of PPAR␣ is the regulation of the rate of fatty acid uptake and their esterification into triglyceride or oxidation, 4 -7 whereas PPAR␥ is classically involved in adipocyte differentiation, regulation of fat storage, and maintenance of glucose homeostasis. 5 The physiological functions of PPAR␦ are instead still unclear, although it is known that this receptor contributes to an inflammatory switch through its association and disassociation with transcriptional repressors. 8 The clinical importance of PPARs originates with fibrates and thiazolidinediones (TZDs), which respectively act on PPAR␣ and PPAR␥ and are used to ameliorate hyperlipidemia and hyperglycemia in subjects with type 2 diabetes mellitus (T2DM). Fibrates, such as gemfibrozil, clofibrate, fenofibrate, and bezofibrate, are drugs that effectively reduce triglycerides (TG) and free fatty acids (FFA) and increase high-density lipoproteins-cholesterol. 9 -12 Fibrates also improve glucose tolerance in T2DM patients, although this activity might be attributable to the fact that some of these compounds also have potential PPAR␥ activity. 13 TZDs, such as rosiglitazone, pioglitazone, troglitazone, and ciglitazone, are insulin-sensitizing drugs and have constituted a major advance in the recent therapeutic management of T2DM. 14 -16
doi:10.1161/circresaha.108.180224 pmid:18596261 fatcat:yzfzw6gonfhadilfghmottmcpq