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Triglyceride-rich lipoprotein interactions with Lp(a)
W J McConathy1, V N Trieu, E Koren
1Texas College of Osteopathic Medicine, Fort Worth 76107.
Insights
Individuals with higher triglycerides (TG) have lower lipoprotein(a) (Lp(a)) levels. This study found no evidence that lipoprotein lipase (LPL) mediates this inverse relationship between TG and Lp(a).
Area of Science:
- Cardiovascular Science
- Lipid Metabolism Research
Background:
- Elevated lipoprotein(a) (Lp(a)) is a risk factor for cardiovascular disease (CVD).
- An inverse relationship exists between plasma triglyceride (TG) levels and Lp(a) levels, but the underlying mechanism is unclear.
Purpose of the Study:
- To investigate the potential role of lipoprotein lipase (LPL) in mediating the inverse relationship between TG and Lp(a).
- To explore the interaction between Lp(a), VLDL-TG, and LPL activity.
Main Methods:
- Assessed Lp(a) and TG levels in subjects with and without coronary artery disease (CAD).
- Evaluated the effect of Lp(a) and LDL2 on VLDL-TG degradation by LPL.
- Performed binding analyses to determine Lp(a) interaction with VLDL and its lipolytic remnants.
Main Results:
- A significantly reduced incidence of increased Lp(a) levels was observed in subjects with TG > 150 mg/dl compared to those with TG < 150 mg/dl, irrespective of CAD status.
- Lp(a) and LDL2 showed minimal inhibition (13%) on VLDL-TG degradation by LPL.
- Binding analyses revealed no significant differences in Lp(a) binding to VLDL and LDL, with lipolysis reducing binding by only 30% at 75% VLDL-TG degradation.
Conclusions:
- The inverse relationship between elevated plasma TG and Lp(a) is not mediated by LPL activation.
- Lp(a) does not appear to bind effectively to VLDL or its lipolytic remnants to influence LPL activity.
- The study hypothesizes that enhanced clearance of TG-rich lipoproteins via receptor-mediated events in individuals with higher Lp(a) may explain the observed inverse relationship.
Abstract:
We found a significantly reduced incidence of increased lipoprotein(a) (Lp(a)) levels in subjects with triglycerides (TG) greater than 150 mg/dl compared with those with TG levels lower than 150 mg/dl. This was the case in patients with angiographically documented coronary artery disease (CAD) and in subjects with no CAD. We explored the potential role of lipoprotein lipase (LPL) in mediating this relationship. Lp(a) and LDL2 exhibited a minimal effect on the rate constant for degradation of VLDL-TG by LPL (13% inhibition). Binding analyses indicated no differences between VLDL and LDL with respect to Lp(a) binding, and lipolysis only reduced binding by 30% at 75% degradation of VLDL-TG. Our study indicates that the inverse relationship between elevated plasma TG and Lp(a) levels is not caused by activation of LPL by Lp(a) either due to failure of Lp(a) to bind to VLDL or its lipolytic remnants. It is hypothesized that this relationship could stem from the enhanced clearance of TG-rich lipoproteins in individuals with higher levels of Lp(a) by receptor-mediated events.