In vitro inhibition of arterial myocyte growth and stimulation of low density lipoprotein metabolism by SIM 6080, a new calcium antagonist

F. Bernini, M. Fantoni, A. Corsini, R. Fumagalli

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

We have investigated thein vitro effect of the new calcium antagonist SIM 6080 on proliferation of rat aortic smooth muscle cells and on LDL receptor-mediated catabolism in human fibroblasts. Verapamil was used as the reference compound. SIM 6080 inhibited the proliferation of rat aortic myocytes in concentrations ranging between 1 and 20, μm. The inhibition, evaluated as cell number and nuclear incorporation of [3H]thymidine, was dose and time dependent; the cell doubling time increased with drug concentrations up to 69 h versus 20 h for controls. Similar results on both LDL pathway and smooth muscle cell proliferation were achieved with verapamil, but higher concentrations were needed. The specific uptake and degradation of125I-LDL was evaluated in human fibroblasts after 48 h incubation with SIM 6080 (1-10 μm). The compound dose dependently enhanced the receptor-mediated125I-LDL uptake, with a fourfold increase as a maximal effect (10 μm); LDL degradation was less sensitive to the drug. The present results provide evidence that the new calcium antagonist SIM 6080 interferesin vitro with processes involved in atherogenesis.

Original languageEnglish
Pages (from-to)27-35
Number of pages9
JournalPharmacological Research
Volume22
Issue number1
DOIs
Publication statusPublished - 1990

Fingerprint

LDL Lipoproteins
Muscle Cells
Calcium
LDL Receptors
Growth
Verapamil
Smooth Muscle Myocytes
Fibroblasts
Pharmaceutical Preparations
Thymidine
Atherosclerosis
Cell Count
Cell Proliferation
In Vitro Techniques
SIM 6080
oxidized low density lipoprotein

Keywords

  • calcium antagonists
  • LDL
  • LDL receptor
  • myocyte proliferation

ASJC Scopus subject areas

  • Pharmacology

Cite this

In vitro inhibition of arterial myocyte growth and stimulation of low density lipoprotein metabolism by SIM 6080, a new calcium antagonist. / Bernini, F.; Fantoni, M.; Corsini, A.; Fumagalli, R.

In: Pharmacological Research, Vol. 22, No. 1, 1990, p. 27-35.

Research output: Contribution to journalArticle

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