The novel compound NO-1886 elevates plasma high-density lipoprotein cholesterol levels in hamsters and rabbits by increasing lipoprotein lipase without any effect on cholesteryl ester transfer protein activity

Abstract

Lipoprotein lipase (LPL) and cholesteryl ester transfer protein (CETP) are determinants of high-density lipoprotein (HDL) cholesterol concentrations in plasma. We have previously reported that NO-1886, by increasing LPL activity, causes elevation of HDL cholesterol levels in rats. In the present study, we studied the effect of NO-1886 on CETP activity in experimental animals. Since previous reports suggest that rats may lack CETP, we examined hamsters and rabbits, as well as rats. We found that NO-1886 increased LPL activity, resulting in elevation of plasma HDL cholesterol in all three animals. We confirmed that rats lack CETP and that both hamsters and rabbits have high CETP activity. NO-1886 had no effect on CETP activity in hamsters and rabbits. These results demonstrate that the compound NO-1886 elevates HDL cholesterol in experimental animals by selectively increasing LPL activity without any effect on CETP. Animals with low CETP and high LPL activities appear to be more sensitive to NO-1886 than those with high CETP and low LPL activities.