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Causes Underlying the Reduced Response to Simvastatin Treatment in Hypercholesterolemic Patients

  • Conference paper
Human Apolipoprotein Mutants III

Part of the book series: NATO ASI Series ((ASIH,volume 73))

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Abstract

Simvastatin, a competitive inhibitor of HMG-CoA reductase, effectively reduces elevated plasma cholesterol levels by up regulating the LDL receptor expression. Therefore in patients whose hypercholesterolemia (HC) is due to a defective LDL-receptor interaction vastatins may not be as effective as expected. To verify this hypothesis we studied the possible causes for the poor response (<15% decrease of LDL cholesterol) to simvastatin (40 mg/die) in 11 HC patients. Biochemical defects were identified in 5 patients. Three patients presented with binding-defective LDL, without the 3500 mutation, and the remaining two had normal LDL but their serum contained factors interfering with the LDL-receptor interaction. From these results we conclude that distinct biochemical defects might contribute to the poor response to simvastatin in hypercholesterolemic patients.

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Author information

Authors and Affiliations

  1. Institute of Pharmacological Sciences, University of Milan, Milan, Italy

    Alberto Corsini Ph.D., Maria Mazzotti Ph.D., Tiziano Zanelli Ph.D., Patrizia Uboldi B.S., Giancarlo Descovish M.D., Agnese Granata B.S. & Remo Fumagalli M.D.

  2. Bollate Hospital, Milan, Italy

    Domenico Sommariva M.D.

  3. Center E. Grossi Paoletti, University of Milan, Italy

    Franco Pazzucconi M.D. & Cesare R. Sirtori M.D.

  4. Atherosclerosis Center and Department of Internal Medicine, S. Orsola Hospital, University of Bologna, Italy

    Antonio Gaddi M.D. & Alberico L. Catapano Ph.D.

Authors
  1. Alberto Corsini Ph.D.
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  2. Maria Mazzotti Ph.D.
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  3. Tiziano Zanelli Ph.D.
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  4. Patrizia Uboldi B.S.
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  5. Domenico Sommariva M.D.
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  6. Franco Pazzucconi M.D.
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  7. Cesare R. Sirtori M.D.
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  8. Antonio Gaddi M.D.
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  9. Giancarlo Descovish M.D.
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  10. Agnese Granata B.S.
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  11. Remo Fumagalli M.D.
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  12. Alberico L. Catapano Ph.D.
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Editor information

Editors and Affiliations

  1. Center E. Grossi Paoletti, Institute of Pharmacological Sciences, University of Milano, Via Balzaretti 9, 20133, Milano, Italy

    Cesare R. Sirtori  & Guido Franceschini  & 

  2. Molecular Disease Branch, National Institutes of Health, NHLBI, 20205, Bethesda, MD, USA

    Bryan H. Brewer Jr.

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© 1993 Springer-Verlag Berlin Heidelberg

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Corsini, A. et al. (1993). Causes Underlying the Reduced Response to Simvastatin Treatment in Hypercholesterolemic Patients. In: Sirtori, C.R., Franceschini, G., Brewer, B.H. (eds) Human Apolipoprotein Mutants III. NATO ASI Series, vol 73. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-84634-2_19

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  • DOI: https://doi.org/10.1007/978-3-642-84634-2_19

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-84636-6

  • Online ISBN: 978-3-642-84634-2

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