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PPARs and Their Emerging Role in Vascular Biology, Inflammation and Atherosclerosis

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Diabetes and Cardiovascular Disease

Part of the book series: Contemporary Cardiology ((CONCARD))

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Abstract

Peroxisome proliferator-activated receptors (PPARs) are powerful, ligand-activated, steroid hormone DNA-binding receptors that determine transcriptional programs related to energy balance and related pathways. Three major isotypes exist: PPAR-γ, PPAR-α, and PPAR-β/δ. PPAR-γ is predominant in adipose tissue promoting insulin sensitivity and weight gain. Also, its presence in the renal tissue promotes water retention. In contrast, PPAR-α receptors are widely present in tissues with high oxidation capacity, stimulating energy burn and decreasing fat storage. PPAR-β/δ is evenly distributed among most tissues where it increases glucose metabolism, decreases lipid accumulation and limits inflammation. Synthetic ligands of PPAR receptors have been widely used as therapeutic agents in diabetes and dyslipidemias. Thiazolidinediones are strong activators of PPAR-γ, while ARBs are weak activators of the same receptor. Fibrates and more recently Omega-3 Fatty Acids are known to activate PPAR-α. Theoretically, PPAR synthetic agonists could have vascular benefits via lowering glucose, raising HDL and decreasing inflammation. Synthetic ligands of PPAR-γ have been shown to decrease surrogate markers of atherosclerosis and inflammation (i.e., foam cell formation, endothelin-1 or CRP levels), this must be gauged against any potential toxicity or adverse event such as weight gain and edema. PPAR-α synthetic ligands potentially limit the inflammatory cytokine induction of adhesion molecules in endothelial cells and NF-kB activation in T-lymphocytes. However, data and clinical trials supporting PPAR agonists have been subjects of controversy. Nonetheless, advancing science will continue to return to PPARs given the centrality of their involvement in metabolism, inflammation and atherosclerosis.

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Authors and Affiliations

  1. St Elizabeth’s Medical Center, Tufts School of Medicine, Boston, MA, USA

    Javier Balda, Argyro Papafilippaki & Michael Johnstone

  2. Steward St. Elizabeth’s Medical Center, Tufts University Medical School, Brighton, MA, USA

    Michael Johnstone

  3. Cardiovascular Division, Steward St. Elizabeth’s Medical Center, Tufts University School of Medicine, Brighton, MA, USA

    Michael Johnstone

  4. Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Jorge Plutzky

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Balda, J., Papafilippaki, A., Johnstone, M., Plutzky, J. (2023). PPARs and Their Emerging Role in Vascular Biology, Inflammation and Atherosclerosis. In: Johnstone, M., Veves, A. (eds) Diabetes and Cardiovascular Disease. Contemporary Cardiology. Humana, Cham. https://doi.org/10.1007/978-3-031-13177-6_4

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  • DOI: https://doi.org/10.1007/978-3-031-13177-6_4

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  • Publisher Name: Humana, Cham

  • Print ISBN: 978-3-031-13176-9

  • Online ISBN: 978-3-031-13177-6

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