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Antiatherosclerotic Drugs: A Critical Assessment

  • Chapter
Drugs Affecting Lipid Metabolism

Part of the book series: Medical Science Symposia Series ((MSSS,volume 2))

Abstract

The increasing knowledge on the processes specific to atherogenesis occurring in the arterial wall and on the physiology of lipid transport, suggest that the antiatherosclerotic pharmacological targets should not be limited to plasma lipids or blood pressure control but should involve a direct effect on the arterial wall. Pivotal roles are played by arterial smooth muscle cells (myocyte, SMC) migration and proliferation, as well as by cholesterol esterification and deposition in arterial macrophages. The importance of mevalonate and of cholesterol biosynthesis in cell growth prompted us to investigate inhibitors of HMGCoA reductase, with in vitro and in vivo models, on SMC proliferation. The results show that fluvastatin (F), simvastatin (S), but not pravastatin (P), decreased the rate of vascular SMC growth and prevented neointimal formation induced by perivascular manipulation of rabbit carotid artery. F and S displayed an inhibitory activity on cholesterol esterification induced by acetylated LDL in mouse peritoneal macrophages. These effects might represent components, along with the inhibition of cholesterol synthesis, of the antiatherosclerotic action of these drugs. Calcium antagonists (CA) may also affect major processes of atheroma formation such as cholesteryl esters metabolism and cell proliferation. Verapamil completely inhibited the ability of acetylated LDL to stimulate cholesterol esterification in macrophages. The dihydropyridine nifedipine was ineffective at this regard. However, the new nifedipine-like derivative lacidipine inhibited esterification in macrophages very efficiently. We also observed that lacidipine and isradipine, another nifedipine-like CA, inhibited proliferation of cultured myocytes. This effect was paralleled by the ability of these compounds to prevent neointimal formation of rabbit carotid artery. In conclusion, a pharmacological control of atherosclerosis may be achieved by directly affecting the processes involved in the atheroma formation. This effect may be obtained with compounds already able to modify major risk factors of atherosclerosis such as hypertension and hypercholesterolemia, or in the future, with new compounds specifically designed as direct antiatherosclerotic drugs.

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Authors
  1. M. Raiteri
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  2. A. Corsini
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  3. M. R. Soma
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  4. E. Donetti
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  5. F. Bernini
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  6. R. Fumagalli
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  7. R. Paoletti
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Editor information

Editors and Affiliations

  1. Istituto di Scienze Farmacologiche, Università di Milano, Via Balzaretti 9, I-20133, Milano, Italy

    A. L. Catapano  & Rodolfo Paoletti (Direttore) &  (Direttore)

  2. Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA

    A. M. Gotto Jr. (Chairman) (Chairman)

  3. Department of Medicine, The Methodist Hospital, 6565 Fannin M.S. A601, Houston, TX, 77030-2797, USA

    Louis C. Smith (Professor of Experimental Medicine) (Professor of Experimental Medicine)

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© 1993 Springer Science+Business Media Dordrecht

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Raiteri, M. et al. (1993). Antiatherosclerotic Drugs: A Critical Assessment. In: Catapano, A.L., Gotto, A.M., Smith, L.C., Paoletti, R. (eds) Drugs Affecting Lipid Metabolism. Medical Science Symposia Series, vol 2. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-1703-6_39

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  • DOI: https://doi.org/10.1007/978-94-011-1703-6_39

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-010-4746-3

  • Online ISBN: 978-94-011-1703-6

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