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.
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%.


CONCLUSIONS
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)
Pedreño
J
J
Department of Biochemistry, Hospital de Son Dureta, Palma de Mallorca, Spain.
Sánchez
J L
JL
Zambón
D
D
Ros
E
E
D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D025782:Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent; D006938:Hyperlipoproteinemia Type II / Q000097:blood*; D008148:Lovastatin / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D017035:Pravastatin / Q000008:administration & dosage / Q000494:pharmacology*; D011973:Receptors, LDL / Q000187:drug effects* / Q000378:metabolism
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011973:Receptors, LDL; D008148:Lovastatin; D025782:Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent; D017035:Pravastatin