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  • Title: In-vitro effect of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors on non-hepatic LDL receptor activity: evidence of lack of stimulatory effect of pravastatin.
    Author: Pedreño J, Sánchez JL, Zambón D, Ros E.
    Journal: Coron Artery Dis; 1994 Dec; 5(12):971-7. PubMed ID: 7728297.
    Abstract:
    BACKGROUND: It is speculated that, as a result of its tissue selectivity, pravastatin may be a safer drug than the lipophilic 3-hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) reductase inhibitors in combination therapy involving drugs with potential muscle toxicity. Several studies have shown specific inhibitory activity on hepatic cholesterogenesis and a potent induction of hepatic low-density lipoprotein (LDL) receptors. However, data about its effect on stimulation of LDL receptor activity on non-hepatic cells are not available. METHODS: Several experiments were carried out in order to assess the in-vitro effect of HMG-CoA reductase inhibitors on the activity of LDL receptors of human non-hepatic cells. Lymphocytes from both normolipidemic controls and patients with heterozygous familial hypercholesterolemia along with human fibroblasts were cultured in both the presence and absence of pravastatin and lovastatin. RESULTS: Pravastatin, at concentrations of 0.25-50 mumol/l, did not enhance the LDL receptor activity of lymphocytes derived from both patients with familial hypercholesterolemia and normolipidemic controls. In contrast, lovastatin, at concentrations of 0.25 mumol/l, increased the LDL receptor activity in both control lymphocytes and lymphocytes from patients with familial hypercholesterolemia by 121% and 148%, respectively. Fibroblast LDL receptor activity was not altered by pravastatin at a concentration of 50 mumol/l, whereas lovastatin at the same concentration increased the LDL uptake by 153%. CONCLUSION: From in-vitro experiments of LDL receptor activity stimulation, we conclude that pravastatin has little effect on non-hepatic cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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