Lipoprotein Lipase Activator NO-1886
http://www.100md.com
Lipoprotein lipase (LPL) is a rate-limiting enzyme that hydrolyzes circulating
triglyceride-rich lipoproteins such as very low-density lipoproteins and chylomicrons. A
decrease in LPL activity is associated with an increase in plasma triglycerides (TG) and a
decrease in plasma high-density lipoprotein cholesterol (HDL-C). The increase in plasma
TG and decrease in plasma HDL-C are risk factors for cardiovascular disease. Tsutsumi et
al. hypothesized that elevating LPL activity would cause a reduction of plasma TG and an
increase in plasma HDL-C, resulting in protection against the development of atherosclerosis.To test this hypothesis, Otsuka Pharmaceutical Factory, Inc. synthesized the LPL activator NO-1886.
NO-1886 increased LPL mRNA and LPL activity in adipose tissue, myocardium and
skeletal muscle, resulting in an elevation of postheparin plasma LPL activity and LPL
mass in rats. NO-1886 also decreased plasma TG concentration and caused a concomitant
rise in plasma HDL-C. Long-term administration of NO-1886 to rats and rabbits with experimental atherosclerosis inhibited the development of atherosclerotic lesions in coronary arteries and aortas. Multiple regression analysis suggested that the increase in
plasma HDL-C and the decrease in plasma TG protect from atherosclerosis. The atherogenic
lipid profile is changed to an antiatherogenic profile by increasing LPL activity, resulting
in protection from of atherosclerosis. Therefore, the LPL activator NO-1886 or
other possible LPL activating agents are potentially beneficial for the treatment of hypertriglyceridemia,hypo-HDL cholesterolemia, and protection from atherosclerosis., 百拇医药
triglyceride-rich lipoproteins such as very low-density lipoproteins and chylomicrons. A
decrease in LPL activity is associated with an increase in plasma triglycerides (TG) and a
decrease in plasma high-density lipoprotein cholesterol (HDL-C). The increase in plasma
TG and decrease in plasma HDL-C are risk factors for cardiovascular disease. Tsutsumi et
al. hypothesized that elevating LPL activity would cause a reduction of plasma TG and an
increase in plasma HDL-C, resulting in protection against the development of atherosclerosis.To test this hypothesis, Otsuka Pharmaceutical Factory, Inc. synthesized the LPL activator NO-1886.
NO-1886 increased LPL mRNA and LPL activity in adipose tissue, myocardium and
skeletal muscle, resulting in an elevation of postheparin plasma LPL activity and LPL
mass in rats. NO-1886 also decreased plasma TG concentration and caused a concomitant
rise in plasma HDL-C. Long-term administration of NO-1886 to rats and rabbits with experimental atherosclerosis inhibited the development of atherosclerotic lesions in coronary arteries and aortas. Multiple regression analysis suggested that the increase in
plasma HDL-C and the decrease in plasma TG protect from atherosclerosis. The atherogenic
lipid profile is changed to an antiatherogenic profile by increasing LPL activity, resulting
in protection from of atherosclerosis. Therefore, the LPL activator NO-1886 or
other possible LPL activating agents are potentially beneficial for the treatment of hypertriglyceridemia,hypo-HDL cholesterolemia, and protection from atherosclerosis., 百拇医药