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Different efflux pathways for high and low density lipoproteins from porcine aortic intima
B G Nordestgaard1, E Hjelms, S Stender
1Department of Clinical Chemistry, University of Copenhagen, Denmark.
Insights
High-density lipoprotein (HDL) cholesteryl ester clears the arterial wall more readily than low-density lipoprotein (LDL) cholesteryl ester. HDL efflux primarily uses outer arterial pathways, while LDL exits via the lumen.
Area of Science:
- Cardiovascular Biology
- Lipid Metabolism
- Arterial Wall Dynamics
Background:
- Understanding lipoprotein movement within the arterial wall is crucial for cardiovascular health.
- High-density lipoproteins (HDL) and low-density lipoproteins (LDL) play distinct roles in cholesterol transport and arterial disease.
Purpose of the Study:
- To investigate the in vivo efflux pathways of HDL and LDL cholesteryl esters from the arterial wall.
- To quantify the differences in arterial wall clearance rates between HDL and LDL.
Main Methods:
- Utilized a surgical pig model with an isolated thoracic aorta segment.
- Employed pulse labeling with 3H-HDL cholesteryl ester and 14C-LDL cholesteryl ester.
- Applied in vivo cold chase experiments to track lipoprotein movement and disappearance.
Main Results:
- HDL cholesteryl ester showed significantly higher intimal clearance (3-7 times greater than LDL).
- A substantial portion of HDL cholesteryl ester (50-95%) penetrated beyond the internal elastic lamina, unlike LDL (<15%).
- After 24 hours, over 80% of both labeled lipoproteins disappeared; HDL was found throughout the wall, while LDL remained in the luminal layer.
Conclusions:
- HDL cholesteryl ester efflux predominantly occurs via vasa vasorum and lymphatics in the outer arterial wall.
- LDL cholesteryl ester primarily exits the intima through the arterial lumen.
- These findings highlight differential efflux mechanisms for HDL and LDL, impacting arterial cholesterol homeostasis.
Abstract:
To study the efflux of high (HDL) and low (LDL) density lipoproteins from the arterial wall in vivo, a surgical model in pigs was used. An isolated segment of the lesion-free thoracic aorta was pulse labeled from the lumen of the artery with 3H-cholesteryl ester labeled HDL and 14C-cholesteryl ester labeled LDL. Subsequently, the labeled aortic segment was exposed to cold chase in vivo. The transfer of HDL cholesteryl ester from plasma into intima expressed as intimal clearance was three to seven times greater than that of LDL cholesteryl ester. At least 50%, but possibly as much as 95%, of the HDL cholesteryl ester that entered the arterial intima during a period of 4 hours penetrated the arterial wall beyond the internal elastic lamina. In contrast, less than 15% of the LDL cholesteryl ester that entered the arterial intima in the same period penetrated beyond the luminal layer. After 24 hours of cold chase in vivo, more than 80% of both labeled HDL esterified cholesterol and labeled LDL esterified cholesterol had disappeared from the arterial wall. Transmural profiles after 9 hours of cold chase showed that labeled HDL was present throughout the entire arterial wall, whereas labeled LDL in quantitative amounts was present only in the luminal layer. The results suggest that the most important efflux route for HDL esterified cholesterol is through the vasa vasorum and lymphatics in the outer media and adventitia, whereas LDL esterified cholesterol predominantly leaves intima via the lumen of the artery.