Low density lipoproteins and atherosclerosis-quantity or quality?

Area of Science:

• Cardiovascular Science
• Lipid Metabolism
• Oxidative Stress Research

Background:

• Oxidative modification of low-density lipoprotein (LDL) is implicated in atherosclerosis development.
• The correlation between LDL's in vitro oxidation susceptibility and in vivo atherogenicity is not always consistent.
• Familial hypercholesterolaemia (FH) presents a complex case with premature atherosclerosis despite less oxidizable LDL particles.

Purpose of the Study:

• To investigate the role of LDL oxidation in atherosclerosis pathogenesis.
• To evaluate the efficacy of antioxidant therapies, like vitamin E and probucol, in managing hypercholesterolaemia and related conditions.
• To determine the optimal therapeutic strategies for different LDL particle profiles and atherosclerosis risk.

Main Methods:

• Analysis of LDL oxidation susceptibility in vitro and its relation to atherogenicity in vivo.
• Assessment of the effects of high-dose, long-term vitamin E and probucol on LDL oxidation and clinical outcomes in familial hypercholesterolaemia.
• Comparison of therapeutic approaches for individuals with large, buoyant LDL versus small, dense LDL particles.

Main Results:

• Large, buoyant LDL particles, typical in FH, are less susceptible to oxidation but associated with severe premature atherosclerosis.
• Vitamin E enhances LDL resistance to oxidation but does not improve xanthoma regression in homozygous FH.
• Small, dense LDL particles are more susceptible to oxidation and linked to increased atherosclerosis risk, even with normal LDL cholesterol levels.

Conclusions:

• In FH, reducing the overall quantity of LDL is the primary therapeutic goal.
• Antioxidant therapy may offer additional benefits for individuals with small, dense LDL particles.
• Current atherosclerosis management should prioritize LDL cholesterol reduction, with antioxidants potentially playing a future complementary role.