Effects of NO-1886, a Lipoprotein Lipase Promoting Agent, on Homozygous and Heterozygous Watanabe Heritable Hyperlipidaemic Rabbits

Summary The novel compound NO-1886 ([4-(4-bromo-2-cyano-phenylcarbamoyl)-benzyl]-phosphonic acid diethyl ester, CAS 133208-93-2) is a lipoprotein lipase (LPL) activaor, and long term administration of NO-1886 protects against the development of experimental atherosclerosis in rats and rabbits. In the present experiments, the effects of this compound were examined in Watanabe heritable hyperlipidaemic (WHHL) rabbits, an animal model for familial hypercholesterolemia lacking low density lipoprotein (LDL) receptors. NO-1886 increased postheparin plasma LPL activity, resulting in a reduction of plasma triglycerides with concomitant elevation of HDL cholesterol in heterozygous WHHL rabbits. However, the compound did not cause any changes in plasma lipids and postheparin plasma LPL activity in homozygous WHHL rabbits. The different responses suggest that the effects of NO-1886 may be either mediated by LDL receptors, or that persistent exposure to extreme hypercholesterolemia might affect the cellular response to this particular compound in homozygous WHHL rabbits.

[1]  S. Miura,et al.  Antiatherogenic effects of a novel lipoprotein lipase-enhancing agent in cholesterol-fed New Zealand white rabbits. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[2]  T. Murase,et al.  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. , 1997, Metabolism: clinical and experimental.

[3]  T. Murase,et al.  Correction of Hypertriglyceridemia with Low High-Density Lipoprotein Cholesterol by the Novel Compound NO-1886, a Lipoprotein Lipase-Promoting Agent, in STZ-Induced Diabetic Rats , 1995, Diabetes.

[4]  K. Iwasaki,et al.  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. , 1993, The Journal of clinical investigation.

[5]  J. Atkinson,et al.  Cholesterol-fed heterozygous Watanabe heritable hyperlipidemic rabbits: a new model for atherosclerosis. , 1989, Atherosclerosis.

[6]  H. Fukuzaki,et al.  Nifedipine suppressed atherosclerosis in cholesterol-fed rabbits but not in Watanabe heritable hyperlipidemic rabbits. , 1987, Artery.

[7]  E. Leitersdorf,et al.  Verapamil Enhances Receptor‐Mediated Endocytosis of Low Density Lipoproteins by Aortic Cells in Culture , 1985, Arteriosclerosis.

[8]  T. Kita,et al.  Deficiency of low density lipoprotein receptors in liver and adrenal gland of the WHHL rabbit, an animal model of familial hypercholesterolemia. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[9]  T. Murase,et al.  A selective decline of postheparin plasma hepatic triglyceride lipase in hypothyroid rats. , 1980, Metabolism: clinical and experimental.

[10]  Y. Watanabe.  Serial inbreeding of rabbits with hereditary hyperlipidemia (WHHL-rabbit). , 1980, Atherosclerosis.

[11]  R. Krauss,et al.  Selective measurement of two different triglyceride lipase activities in rat postheparin plasma. , 1973, Journal of lipid research.