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Ppar-Alpha in Lipid and Lipoprotein Metabolism, Vascular Inflammation and Atherosclerosis

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Atherosclerosis, Hypertension and Diabetes

Part of the book series: Progress in Experimental Cardiology ((PREC,volume 8))

Abstract

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear receptor superfamily, PPAR-alpha is highly expressed in liver, skeletal muscle, kidney, heart and the vascular wall. PPARs are activated by fattyacid derivatives and pharmacological agents such as fibrates for PPAR-alpha. PPAR- alpha controls intra-and extracellular lipid metabolisms. Fibric acids decrease triglyceride concentrations by increasing the expression of lipoprotein lipase and decreasing apo C-III concentration. Furthermore, they increase HDL-cholesterol by increasing the expression of apo A-I and apo A-II. In addition, PPARs also modulate the inflammatory response. PPAR activators have been shown to exert anti-inflammatory activities in various cell types by inhibiting the expression of proinflammatory genes such as cytokines, metalloproteases and acute-phase proteins. PPARs negatively regulate the transcription of inflammatory response genes by antagonizing the AP-1, nuclear factor-κB (NF-κB), signal transducer and activator of transcription (STAT) and nuclear factor of activated T-cells (NFAT) signalling pathways and by stimulating the catabolism of proinflammatory eicosanoids. PPAR-alpha activators (gemfibrozil) decrease the risk of coronary heart disease in patients with normal LDL-cholesterol and low HDL-cholesterol (VA-HIT) and they slow the progression of premature coronary atherosclerosis (BECAIT) (bezafibrate), particularly in patients with type 2 diabetes (DAIS) (fenofibrate).

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Authors and Affiliations

  1. Unité de Recherche sur les Lipoprotéines et l’Athérosclérose—Inserm U545—Institut Pasteur et Université de Lille 2—Faculté de Pharmacie—Lille, France

    Jean-Charles Fruchart, Bart Staels & Patrick Duriez

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  1. Jean-Charles Fruchart
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Editors and Affiliations

  1. Division of Stroke & Vascular Disease, St. Boniface General Hospital Research Centre, Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Grant N. Pierce PhD, FACC (Professor & Director) (Professor & Director)

  2. Department of Medicine, Jikei University School of Medicine, Tokyo, Japan

    Makoto Nagano MD, PhD (Professor Emeritus) (Professor Emeritus)

  3. Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Peter Zahradka PhD (Associate Professor) & Naranjan S. Dhalla PhD, MD (Hon), DSc (Hon) (Distinguished Professor and Director) (Associate Professor) &  (Distinguished Professor and Director)

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Fruchart, JC., Staels, B., Duriez, P. (2003). Ppar-Alpha in Lipid and Lipoprotein Metabolism, Vascular Inflammation and Atherosclerosis. In: Pierce, G.N., Nagano, M., Zahradka, P., Dhalla, N.S. (eds) Atherosclerosis, Hypertension and Diabetes. Progress in Experimental Cardiology, vol 8. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-9232-1_1

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