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HMG-CoA Reductase Inhibitors pp 35–54Cite as

Birkhäuser

Sterol-regulatory element binding proteins (SREBPs): gene-regulatory target of statin action

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Part of the book series: Milestones in Drug Therapy MDT ((MDT))

Abstract

Several clinical studies have demonstrated over the last few years that efficient reduction of plasma cholesterol significantly reduces the incidence of clinical overt cardiovascular complications, like myocardial infarction or stroke, but has almost no effect on angiographically determined luminal diameter of coronary arteries. These, as well as many morphological and molecular studies, have led to a new paradigm of coronary heart disease, i.e., clinical prognosis is not mainly determined by the extent of a single stenosis, but by the number and biological nature of atherosclerotic plaques [ 1– 7]. Considering biological and morphological features of atherosclerotic plaques, two types can be differentiated, stable and instable or vulnerable plaques. Vulnerable plaques are characterized by a large lipid-rich core with surrounding inflammation and a thin friable overlying fibrous cap susceptible to rupture or fissuring, thereby being a focus of high risk for thrombus formation. Rupture with consecutive thrombus formation can cause an acute coronary syndrome, such as unstable angina or myocardial infarction. So far reduction of plasma cholesterol by lipid-lowering therapy has been shown to reduce the lipid-rich core as well as inflammatory reactions, affect pro-coagulatory activity and increase extracellular matrix content and improve pardoxic vasocontriction by endothelial dysfunction. This might be due to efficient plasma cholesterol lowering and/or possible direct effects of statins on the vessel wall.

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  1. Klinik II und Poliklinik für Innere Medizin der Universität zu Köln, D-50924, Köln, Germany

    Wilhelm Krone

  2. Abteilung Klinische Biochemie und Pathobiochemie, Deutsches Diabetes-Forschungsinstitut an der Heinrich-Heine-Universität Düsseldorf, Auf’m Hennekamp 65, 40225, Düsseldorf, Germany

    Jörg Kotzka & Dirk Müller-Wieland

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  1. Institute for Clinical Chemistry and Laboratory Medicine, University Regensburg, Franz-Josef-Strauss-Allee 11, D-93053, Regensburg, Germany

    Gerd Schmitz

  2. Johannes Gutenberg-Universität Mainz Klinikum, Institut für Klinische Chemie und Laboratoriumsmedizin, D-55101, Mainz, Germany

    Michael Torzewski

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Kotzka, J., Krone, W., Müller-Wieland, D. (2002). Sterol-regulatory element binding proteins (SREBPs): gene-regulatory target of statin action. In: Schmitz, G., Torzewski, M. (eds) HMG-CoA Reductase Inhibitors. Milestones in Drug Therapy MDT. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-8135-7_3

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