Accumulation of lipoprotein fractions and subfractions in the arterial wall, determined in an in vitro perfusion system
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T Björnheden1, A Babyi, G Bondjers
1Wallenberg Laboratory for Cardiovascular Research, University of Göteborg, Sahlgren's Hospital, Gothenburg, Sweden. tom.bjornheden@wlab.wall.gu.se
Insights
Denser low-density lipoprotein (LDL) particles are linked to higher coronary artery disease (CAD) risk. This study shows smaller, denser LDL subfractions are taken up more by arterial tissue, potentially increasing lipid load and CAD risk.
Area of Science:
- Cardiovascular Science
- Lipoprotein Metabolism
- Atherosclerosis Research
Background:
- Elevated levels of dense low-density lipoprotein (LDL) subfractions in plasma are associated with increased risk of coronary artery disease (CAD).
- This association may stem from increased infiltration of these smaller, denser LDL particles into the arterial intima.
- Lipoprotein particle size is hypothesized to inversely correlate with its inflow into arterial tissue.
Purpose of the Study:
- To investigate the role of lipoprotein particle size in uptake by the arterial wall.
- To evaluate the uptake of different lipoprotein classes and LDL subfractions in atherosclerotic rabbit aorta.
- To determine if denser LDL subfractions contribute to increased lipid accumulation in the arterial wall.
Main Methods:
- Utilized an in vitro perfusion system with aortic intima-media from rabbits with experimentally induced atherosclerosis.
- Studied the uptake of human very-low-density lipoprotein (VLDL), LDL, high-density lipoprotein (HDL), and LDL subfractions (LDL1 and LDL2) in both lesion and non-involved areas.
- Quantified lipoprotein uptake in terms of volume per mass of tissue per hour (nl/mg wet wt./h).
Main Results:
- Lipoprotein uptake into arterial tissue was significantly influenced by particle size, with smaller particles showing higher uptake rates.
- Uptake rates varied by particle type: VLDL (7.6 plaque, 3.8 other), LDL (25 plaque, 4.1 other), and HDL (58 plaque, 12 other) nl/mg wet wt./h.
- The denser LDL2 subfraction exhibited 1.5-1.9 times higher uptake than the less dense LDL1 subfraction.
- LDL uptake was substantially higher in plaque areas (576 nl/mg wet wt.) compared to non-involved areas (48 nl/mg wet wt.), indicating both rapid clearance and large distribution volume in plaques.
Conclusions:
- Particle size is a critical determinant of lipoprotein clearance into arterial tissue, with smaller particles like denser LDL being more readily taken up.
- The increased uptake of denser LDL subfractions (LDL2 > LDL1) supports the hypothesis that enhanced lipid loading in the arterial wall is a mechanism linking denser LDL to CAD.
- The significantly greater LDL uptake and distribution volume in atherosclerotic plaques compared to normal arterial tissue highlight the role of plaque characteristics in lipoprotein accumulation.
Abstract:
A large proportion of a dense subfraction of LDL in plasma is coupled with an increased risk of coronary artery disease, CAD. This may reflect an increased inflow of such LDL subfractions into the intima, since the inflow of lipoproteins is supposed to be inversely related to the size of the particles. In order to evaluate this possibility we used an in vitro perfusion system for aortic intima-media from rabbits with experimental atherosclerosis. The uptake of human VLDL, LDL, HDL and subfractions of LDL (LDL1, 1.019-1.035 and LDL2, 1.035-1.063 g/ml) in lesions and non-involved areas was studied. Our results indicate that particle size is an important factor for the clearance of lipoproteins into the arterial tissue, both for plaques (VLDL 7.6, LDL 25, HDL 58 nl/mg wet wt./h) and in other areas (VLDL 3.8, LDL 4.1, HDL 12 nl/mg wet wt./h). Interestingly, the uptake of LDL2 was as much as 1.5-1.9 times higher than LDL1. This supports the view that an increased lipid load in the arterial wall may be one mechanism behind the association between denser LDL and CAD. Our data also suggest that the difference between LDL uptake in plaque (576 nl/mg wet wt.) and other areas (48 nl/mg wet wt.) not only reflects a rapid clearance but a large distribution volume of the intima (plaque > 60%, non-involved areas 5.7%).