PPAR Ligands: Are They Potential Agents for Cardiovascular Disorders?

Abstract

Peroxisome proliferator activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors. The PPAR subfamily consists of three members: PPARα, PPARγ, and PPARβ/δ. Fibrates are acting via PPARα, and they are used as lipid-lowering agents. PPARγ agonists reduce insulin resistance and have been used in the treatment of type 2 diabetes. As the knowledge of the pleiotropic effects of these agents advances, further potential indications are being revealed, including a novel role in the management of cardiovascular disorders (CVD). PPARα/γ dual agonists are currently under development and hold considerable promise in the management of type 2 diabetes and provide an effective therapeutic option for treating the multifactorial components of CVD. Several experimental and clinical evidences elucidated the beneficial effects of PPAR ligands in prevention and treatment of various CVD. However, PPARα and PPARγ agonists have been shown to be proinflammatory and proatherogenic in a few studies. Further, PPARγ ligands have been noted to be involved in the pathogenesis of congestive heart failure. These controversial results obtained from a few studies created further complication in understanding the role of PPARs. The function of PPARδ and its potential as a cardiovascular therapeutic target are currently under investigation. The present review focuses on the merits and limitations of PPAR agonists with regard to their use in CVD.

Taiwanofungus camphoratusActivates Peroxisome Proliferator-Activated Receptors and Induces Hypotriglyceride in Hypercholesterolemic Rats

“…25,26) Activation of PPAR promotes both lipid storage and lipogenesis, which involves the expression of such genes as aP2, CD36, SCD-1, lipoprotein lipase, and fatty acid transport protein 1. The expression of these genes increases the triglyceride content of adipose tissue and decreases triglyceride and free fatty acids in the circulation, liver and muscles, and finally results in the redistribution of body-wide lipids.…”

Effect of Peroxisome Proliferator—Activated Receptor Gamma Agonists on Myofibroblast Differentiation and Collagen Production in Nasal Polyp—Derived Fibroblasts

“…13 The endogenous ligands of PPARγ include 15d-PGJ2, lysophosphatidic acid, and nitrolinoleic acid. 20 PPARγ can also be activated by synthetic ligands, including the thiazolidinedione class of clinically useful insulin-sensitizing drugs such as rosiglitazone and ciglitazone. 20 The anti-inflammatory properties of PPARγ ligands have been well described.…”

Porównanie wpływu leczenia hipolipemicznego na wydzielanie cytokin prozapalnych u kobiet i mężczyzn z cukrzycą typu 2 i dyslipidemią aterogenną

“…How ever, the clinical benefits associated with hypolipidaemic agents seem to result in part from their extralipid, so-called pleiotropic effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) and peroxisome proliferator-activated receptor-a (PPAR-a) activators (fibrates). These agents were found to produce anti-inflammatory, antioxidant, and antithrombotic properties, to regulate the growth and migration of smooth muscle cells and to improve endothelial function [4][5][6][7]. These effects may explain why statins are effective in reducing cardiovascular events in high-risk subjects without elevated LDL-cholesterol, including type 2 diabetes patients [8] and apparently healthy persons with elevated Creactive protein (CRP) levels [9], whereas fibrates are effective in patients with low low-density lipoprotein (HDL) cholesterol and metabolic syndrome [10,11].…”