The effect of atorvastatin on erythrocyte membranes and serum lipids in patients with type-2 hypercholesterolemia.
BACKGROUND
. The beneficial effects of statins on clinical events may involve mechanisms that modify endothelial dysfunction, plaque stability, thrombus formation, and inflammatory responses. To determine the effect of atorvastatin on blood rheology in patients with familial hypercholesterolemia (FH), we prospectively studied serum lipid concentration, red cell cholesterol content, lipid peroxidation and erythrocyte membrane fluidity. The aim of this paper was to evaluate the effects of atorvastatin therapy on the erythrocyte membrane structure and the hypolipemic efficacy in patients with FH. MATERIALS, METHODS AND SUBJECTS STUDIED:. The study involved 31 patients with FH and 20 healthy individuals as a control group. The program lasted 20 weeks. For the first 8 weeks, the patients were on a hypolipemic diet only and for the subsequent 12 weeks, alongside the diet they were given 10 mg atorvastatin per day. Laboratory tests were carried out before and after 4 weeks and 12 weeks of the pharmacological treatment. Erythrocyte membrane fluidity was determined using the spin labeled method. The peroxidation of lipids was measured in whole erythrocytes as well as in erythrocyte plasma membranes by means of the thiobarbituric acid technique.


RESULTS
. Treatment with atorvastatin reduced serum total cholesterol concentration from 310+/-29 mg/dl in a basal situation to 203+/-34 mg/dl ( P<0.001) at the end of the treatment and low-density lipoprotein (LDL) cholesterol concentration from 225+/-30 mg/dl to 126+/-30 mg/dl ( P<0.001), respectively. The changes observed in the plasma lipids correlate with a significant decrease in erythrocyte membrane cholesterol, from 2.24+/-1.69 to 1.17+/-0.75 mg/mg protein ( P<0.001) after 12 weeks of treatment. The lipid peroxidation in membranes of erythrocytes was lowered from the basal value 0.171+/-0.097 to 0.100+/-0.024 mmol/mg protein ( P<0.05) after 4 weeks of treatment and to 0.057+/-0.020 mmol/mg protein ( P<0.001) after 12 weeks of treatment, and in total erythrocytes from 4.78+/-1.49 to 3.99+/-1.39 mmol/g Hb ( P<0.02) and 2.43+/-0.87 mmol/g Hb ( P<0.001), respectively. The membrane fluidity was estimated by means of parameter S at the depth of the fifth carbon atom. Atorvastatin in hypercholesterolemic erythrocytes enhances the fluidity of the superficial layer from 0.758+/-0.009 up to the values observed in the control group 0.744+/-0.009 ( P<0.001). There is no impact on the microviscosity of the hydrophobic core observed.


CONCLUSIONS
. Our findings suggest that the atorvastatin therapy reverses the alteration of erythrocyte plasma membrane properties. It may improve blood rheology in patients with FH. This improvement in blood properties may contribute to the well-known beneficial effects of atorvastatin on cardiovascular risk in patients with severe hyperlipidemia and atherosclerotic vascular disease.
Koter
M
M
Department of Environment Pollution Biophysics, University of Lodz, 12/16 Banacha St., 90-347 Lodz, Poland. koterm@biol.uni.lodz.pl
Broncel
M
M
Chojnowska-Jezierska
J
J
Klikczynska
K
K
Franiak
I
I
D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000069059:Atorvastatin; D008078:Cholesterol, LDL / Q000097:blood; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000178:diet therapy / Q000188:drug therapy*; D015227:Lipid Peroxidation / Q000187:drug effects; D008055:Lipids / Q000097:blood*; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects; D008875:Middle Aged; D011446:Prospective Studies; D011758:Pyrroles / Q000627:therapeutic use*; D016896:Treatment Outcome
D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D008055:Lipids; D011758:Pyrroles; D000069059:Atorvastatin