Key result
Overexpression of human LPL in WHHL rabbits reduced total cholesterol by 64% and triglycerides by 91%, but resulted in a two-fold increase in aortic atherosclerosis compared to non-transgenic rabbits.
Why the study?
Does overexpression of human LPL affect plasma lipids and aortic atherosclerosis in LDL receptor-deficient WHHL rabbits?
Population
Transgenic Watanabe heritable hyperlipidemic (WHHL) rabbits (LDL receptor deficient)
Comparison
Overexpression of human lipoprotein lipase (LPL) vs Non-transgenic WHHL rabbits
Design
Preclinical
Authors
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Cautions LPL-targeted strategies in LDLR deficiency despite lipid lowering; leaves open mechanisms and human translation.
Does overexpression of human LPL affect plasma lipids and aortic atherosclerosis in LDL receptor-deficient WHHL rabbits?
Effect estimate: 2-fold increase
In the setting of LDL receptor deficiency, increased LPL activity improves hyperlipidemia but paradoxically accelerates atherosclerosis by increasing the generation of atherogenic small dense LDL particles.
Koike et al. (2004) studied Atherosclerosis and hyperlipidemia. Overexpression of human lipoprotein lipase (LPL) vs. Non-transgenic WHHL rabbits was evaluated on Aortic atherosclerosis (2-fold increase). Overexpression of human LPL in WHHL rabbits reduced total cholesterol by 64% and triglycerides by 91%, but resulted in a two-fold increase in aortic atherosclerosis compared to non-transgenic rabbits.
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