Dh. Pogue et al., EFFECT OF LOVASTATIN ON CHOLESTEROL CONTENT OF CARDIAC AND RED-BLOOD-CELL MEMBRANES IN NORMAL AND CARDIOMYOPATHIC HAMSTERS, The Journal of pharmacology and experimental therapeutics, 273(2), 1995, pp. 863-869
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
.