The peroxisome proliferator‐activated receptors in cardiovascular diseases: experimental benefits and clinical challenges

  title={The peroxisome proliferator‐activated receptors in cardiovascular diseases: experimental benefits and clinical challenges},
  author={Wai San Cheang and Xiao Yu Tian and Wing Tak Wong and Yu Huang},
  journal={British Journal of Pharmacology},
The peroxisome proliferator‐activated receptors, PPARα, PPARβ/δ and PPARγ, are ligand‐activated transcriptional factors belonging to the nuclear receptors superfamily and they are known to play important roles in glucose and lipid metabolism. Experimental studies in animal models of metabolic diseases have also revealed that activation of PPARs protects against the vascular complications of diabetes, hypertension, atherosclerosis, myocardial infarction and stroke, through exerting their anti… 

Antihypertensive effects of peroxisome proliferator-activated receptor-β/δ activation.

Preclinical studies suggest that pharmacological PPARβ/δ activation induces antihypertensive effects in direct and indirect models of hypertension, associated with end-organ damage protection and evidence from clinical trials is examined.

The Opportunities and Challenges of Peroxisome Proliferator-Activated Receptors Ligands in Clinical Drug Discovery and Development

84 types of PPAR synthetic ligands introduced to date for the treatment of metabolic and other diseases are summarized and a comprehensive analysis of the current applications and problems of these ligands in clinical drug discovery and development is provided.

The Positive Regulation of eNOS Signaling by PPAR Agonists in Cardiovascular Diseases

The most meaningful and up-to-date in vitro and in vivo studies of the regulation of NO production performed by different PPAR agonists are reported, providing insights into the molecular mechanisms of PPAR-mediated eNOS activation.

Peroxisome proliferator‐activated receptors in cardiac energy metabolism and cardiovascular disease

The role of isoforms of PPAR in the cardiomyocytes energy balance and CVD is discussed in the hope that the knowledge will help in the synthesis of ligands for their partial activation in order to render energy Balance and protection from CVD.

Pharmacological Activation of Peroxisome Proliferator-Activated Receptor {Delta} Increases Sphingomyelin Synthase Activity in THP-1 Macrophage-Derived Foam Cell

This study represents the first to suggest that PPARδ activation may be a potential risk of AS through enhancing activity of SMS2 through the influence of GW501516 on SMS and its product molecule SM.

REVIEW Small Vessels-Big Problems: Novel Insights into Microvascular Mechanisms of Diseases Antihypertensive effects of peroxisome proliferator-activated receptor- (cid:2) / (cid:3) activation

Mechanistic insights into the antihypertensive effects of PPAR ( cid:2) / (cid:3) activators are reviewed, including molecular and functional mechanisms.

Novel Phenyldiazenyl Fibrate Analogues as PPAR α/γ/δ Pan-Agonists for the Amelioration of Metabolic Syndrome.

Two series of new phenyldiazenyl fibrate derivatives of GL479, a previously reported PPARα/γ dual agonist, were synthesized and tested, and compound 12a was identified as a PPAR pan-agonist with moderate and balanced activity on the three PPAR isoforms.

Targeting endothelial dysfunction and inflammation.



PPARalpha and PPARgamma dual agonists for the treatment of type 2 diabetes and the metabolic syndrome.

Future development of dual PPARalpha/gamma agonists with selective PPAR modulator activity appears appropriate and should be feasible.

The PPAR-RXR Transcriptional Complex in the Vasculature: Energy in the Balance

Detailed data establishing a key role for PPARs and RXRs in energy balance, inflammation, and vascular biology stands separately from the clinical experience with any given synthetic PPAR agonist.

Interference with PPAR gamma function in smooth muscle causes vascular dysfunction and hypertension.

PPARδ regulates multiple proinflammatory pathways to suppress atherosclerosis

It is shown here that orally active PPARδ agonists significantly reduce atherosclerosis in apoE−/− mice and suggest PParδ-selective drugs as candidate therapeutics for Atherosclerosis.

Three-in-one agonists for PPAR-α, PPAR-γ, and PPAR-δ from traditional Chinese medicine

The top two TCM candidates are proposed as potential lead compounds in developing agonists targeting PPARs protein for treating metabolic syndrome.

The Peroxisome Proliferator Activated Receptor‐γ Pioglitazone Improves Vascular Function and Decreases Disease Activity in Patients With Rheumatoid Arthritis

Addition of pioglitazone to RA standard of care significantly improves aortic elasticity and decreases inflammation and disease activity with minimal safety issues.

Peroxisome-proliferator-activated receptor delta activates fat metabolism to prevent obesity.

It is shown here that targeted activation of PPARdelta in adipose tissue specifically induces expression of genes required for fatty acid oxidation and energy dissipation, which in turn leads to improved lipid profiles and reduced adiposity.

Reduction of Atherosclerosis by the Peroxisome Proliferator-activated Receptor α Agonist Fenofibrate in Mice*

Analysis of the effect of treatment with the PPARα agonist fenofibrate on the development of atherosclerotic lesions in apolipoprotein (apo) E-deficient mice and human apoA-I transgenic apoE- deficient mice fed a Western diet indicates that this agonist reduces atherosclerosis.