THE NOVEL COMPOUND NO-1886 INCREASES LIPOPROTEIN-LIPASE ACTIVITY WITH RESULTING ELEVATION OF HIGH-DENSITY-LIPOPROTEIN CHOLESTEROL, AND LONG-TERM ADMINISTRATION INHIBITS ATHEROGENESIS IN THE CORONARY-ARTERIES OF RATS WITH EXPERIMENTAL ATHEROSCLEROSIS

We have discovered a novel compound, NO-1886, which possesses a powerful lipoprotein lipase (LPL) activity-increasing action. Administration of NO-1886 increased LPL activity in the postheparin plasma, adipose tissue, and myocardium of rats, and produced a reduction in plasma triglyceride levels with concomitant elevation of HDL cholesterol levels. Administration of NO-1886 increased LPL enzyme mass in postheparin plasma and mRNA activity in epididymal adipose tissue, and it was concluded that the mode of action of this compound is stimulation of tissue LPL synthesis. We also conducted long-term studies to assess the impact of increases in LPL activity and HDL levels on the development of atherosclerotic lesions in rats. Administration of NO-1886 for as long as 90 d significantly decreased the degree of atherosclerotic changes in the coronary arteries of vitamin D2-treated, cholesterol-fed rats. Statistical analysis indicated that increased concentration of HDL is the factor contributing mostly to the prevention of coronary artery sclerosis. In summary, the results of our study indicate that compound NO-1886 increases LPL activity, causing an elevation in HDL levels, and that long-term administration of NO-1886 to rats with experimental atherosclerosis provides significant protection against the development of coronary artery lesions.