Arterial permeability and efflux of apolipoprotein B-containing lipoproteins assessed by in situ perfusion and three-dimensional quantitative confocal microscopy

Abstract

Objectives: There is accumulating evidence that an increased risk of cardiovascular disease (CVD) is not simply caused by the degree of arterial exposure to plasma lipoproteins but, in addition, is determined by the affinity of the vasculature for different lipoprotein phenotypes. In this study we compare the delivery and efflux of 2 atherogenic lipoproteins to further understand the factors that regulate cholesterol accumulation in early atherogenesis.

Methods and results: Lipoproteins containing apolipoprotein (apo) B100 (a low-density lipoprotein [LDL]) and apoB48 (chylomicron remnants) were isolated and differentially conjugated with fluorophores and simultaneously perfused at equivalent concentrations in situ through rabbit carotid vessels. Perfusion systems were established to quantify and differentiate between lipoprotein arterial delivery and efflux. The total average rate of delivery for LDL particles (23 nm) compared with chylomicron remnants (50 nm) was 4427 particles/min(-1) per microm3 and 452 particles/min(-1) per microm3, respectively. In contrast, the average rate of efflux was 3195 particles/min(-1) per microm3 and 163 particles/min(-1) per microm3 for LDL and chylomicron remnants, respectively.

Conclusions: Results indicate that although LDL particles have a higher rate of delivery, they efflux more readily from arterial tissue compared with the larger chylomicron remnants. Collectively, our findings highlight that lipoproteins permeate through arterial tissue differently and may be dependent on the phenotype and potential interactions with extracellular matrix components.