EFFECT OF LOVASTATIN ON CHOLESTEROL CONTENT OF CARDIAC AND RED-BLOOD-CELL MEMBRANES IN NORMAL AND CARDIOMYOPATHIC HAMSTERS

Lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A, is used therapeutically to lower plasma cholesterol levels. However, the effect of this therapy on cell membrane cholesterol in vivo is not kno wn. The goal of this study was to investigate whether lovastatin treat ment of hamsters decreases cholesterol in cardiac cell membranes and i n red blood cell (RBC) membranes. Because abnormal cellular Ca++ regul ation has been associated with altered membrane cholesterol in hearts of cardiomyopathic (CM) hamsters, we also measured the cholesterol con tent of cardiac and RBC membranes from lovastatin-treated and untreate d Bio 14.6 CM hamsters to determine whether any differences existed wi th respect to normals. Sarcolemma-enriched cardiac membranes and RBC m embranes were obtained from 42 to 45-day normal and CM hamsters after 13 days of lovastatin treatment (0.1% of food/day) and from untreated normal and CM hamsters. Plasma cholesterol, membrane cholesterol/phosp holipid (C/PL) ratio and cholesterol per milligram of membrane protein (C/prot) were determined. In hearts from untreated CM hamsters, C/pro t was significantly lower (P <.05) than in untreated normals. Lovastat in decreased plasma cholesterol by 76% and 81% in normal and CM hamste rs, respectively (P <.001), but after lovastatin treatment, there was no significant change in C/PL or C/prot in cardiac membranes from eith er strain; there was also no significant decrease in C/prot or in C/PL of RBC membranes from normals or C/PL of CM hamster RBC membranes. Ho wever, lovastatin feeding resulted in a significant (P <.01) 24% decre ase in C/prot of CM RBC membranes. We conclude that membrane cholester ol is effectively maintained within narrow limits in the normal hamste r heart and in circulating cells from normal hamsters, despite large c hanges in plasma cholesterol. However, RBCs from CM hamsters demonstra te increased susceptibility to fluctuations in plasma cholesterol comp ared with RBCs from the normal strain. Finally, the decreased C/prot i n untreated CM hearts compared with untreated normals may contribute t o the Ca++ deficit that we have recently reported in CM hamster hearts .