Serum from hypercholesterolemic patients treated with atorvastatin or simvastatin inhibits cultured human smooth muscle cell proliferation

Lorenzo Arnaboldi, Massimiliano Guzzetta, Franco Pazzucconi, Giovanni Radaelli, Rodolfo Paoletti, Cesare R. Sirtori, Alberto Corsini

Research output: Contribution to journalArticle

Abstract

We evaluated the pharmacological activity of whole-blood serum from atorvastatin- vs. simvastatin- (both 40 mg/day) treated hypercholesterolemic patients (n = 10) on cultured smooth muscle cell (SMC) proliferation and cholesterol biosynthesis, as related to lipid-lowering effect. Patients received either single or 2-weeks repeated doses of both simvastatin and atorvastatin, following a randomised, double-blind, cross-over design. Blood samples were collected before drug administration and at the scheduled intervals after administration, and the obtained serum was separated by centrifugation, sterilized and frozen until assayed. Cultured SMC were supplemented with medium plus 15% of separate serum sampled from the patients, and grown for 72 h. Proliferation was assayed by a Coulter Counter, while cholesterol biosynthesis was measured by the incorporation of 14C-acetate into cholesterol, under the same experimental conditions. Atorvastatin was more active vs. simvastatin in reducing total- (-28.3% vs. -20.7%; p = 0.045) and LDL-cholesterol (-39.8% vs. -30.1%; p = 0.011) after a 2-weeks regimen. Serum from atorvastatin-treated patients inhibited SMC proliferation vs. t = 0 after both single (AUC -21.6%) and repeated (AUC -26.9%) doses, while serum from simvastatin-treated patients inhibited SMC proliferation only after repeated doses (AUC -24.5%). Interestingly, in the same experimental conditions, the serum concentrations of both statins (and of their active metabolites) were constantly below the detection limits, as shown from the lack of inhibition of cholesterol biosynthesis. The absence of any significant association between the lipid-lowering effects and the inhibition of SMC proliferation, together with no detectable active statin in the serum, suggests that these effects are elicited through independent mechanisms.

Original languageEnglish
Pages (from-to)503-508
Number of pages6
JournalPharmacological Research
Volume56
Issue number6
DOIs
Publication statusPublished - Dec 2007

Keywords

  • Atherosclerosis
  • Cell proliferation
  • Hypercholesterolemia
  • Pleiotropic effects of statins

ASJC Scopus subject areas

  • Pharmacology

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