Lipoprotein lipase and atherosclerosis.

Area of Science:

• Biochemistry
• Cardiovascular Science
• Metabolic Research

Background:

• Lipoprotein lipase (LPL) is crucial for triglyceride metabolism, influencing triglyceride-rich lipoproteins like VLDL and chylomicrons.
• Decreased LPL activity correlates with elevated plasma triglycerides (TG) and reduced HDL cholesterol, both risk factors for coronary heart disease.
• The role of LPL in atherosclerosis is debated, with conflicting evidence suggesting it may promote or protect against the condition.

Purpose of the Study:

• To investigate the hypothesis that increasing LPL activity protects against atherosclerosis by modulating plasma lipid profiles.
• To evaluate the effects of the LPL activator NO-1886 on lipid levels and atherosclerotic lesion development in animal models.

Main Methods:

• Administration of the LPL activator NO-1886 to rats and rabbits with experimental atherosclerosis.
• Measurement of LPL mRNA and activity in various tissues, postheparin plasma LPL activity, and LPL mass.
• Analysis of plasma TG and HDL cholesterol levels, and assessment of atherosclerotic lesion progression in coronary arteries and aortae.

Main Results:

• NO-1886 increased LPL mRNA and activity in multiple tissues, elevating postheparin plasma LPL activity and mass in rats.
• NO-1886 administration led to decreased plasma TG levels and a concurrent increase in HDL cholesterol.
• Long-term NO-1886 treatment inhibited the development of atherosclerotic lesions in the coronary arteries and aortae of rats and rabbits.

Conclusions:

• Elevating LPL activity favorably shifts the lipid profile from atherogenic to anti-atherogenic by reducing TG and increasing HDL cholesterol.
• The study provides strong evidence that high LPL activity is anti-atherogenic, offering protection against atherosclerosis development.
• Conversely, low LPL activity appears to be atherogenic, contributing to the progression of atherosclerotic disease.