Vasculoprotective properties of plasma lipoproteins from brown bears (Ursus arctos)

Matteo Pedrelli,Paolo Parini,Jonas Kindberg,Jon M Arnemo,Ingemar Bjorkhem,Ulrika Aasa,Maria Westerståhl,Anna Walentinsson,Chiara Pavanello,Marta Turri,Laura Calabresi,Katariina Öörni,Gérman Camejo,Ole Fröbert,Eva Hurt-Camejo

doi:10.1016/j.jlr.2021.100065

Abstract

Plasma cholesterol and triglyceride (TG) levels are twice as high in hibernating brown bears (Ursus arctos) than healthy humans. Yet, bears display no signs of early stage atherosclerosis development when adult. To explore this apparent paradox, we analyzed plasma lipoproteins from the same 10 bears in winter (hibernation) and summer using size exclusion chromatography, ultracentrifugation, and electrophoresis. LDL binding to arterial proteoglycans (PGs) and plasma cholesterol efflux capacity (CEC) were also evaluated. The data collected and analyzed from bears were also compared with those from healthy humans. In bears, the cholesterol ester, unesterified cholesterol, TG, and phospholipid contents of VLDL and LDL were higher in winter than in summer. The percentage lipid composition of LDL differed between bears and humans but did not change seasonally in bears. Bear LDL was larger, richer in TGs, showed prebeta electrophoretic mobility, and had 5–10 times lower binding to arterial PGs than human LDL. Finally, plasma CEC was higher in bears than in humans, especially the HDL fraction when mediated by ABCA1. These results suggest that in brown bears the absence of early atherogenesis is likely associated with a lower affinity of LDL for arterial PGs and an elevated CEC of bear plasma.

Highlights

We report on the lipoprotein composition and two functional properties that appear to modulate early atherogenesis in humans and preclinical mammalian models: the association of LDL with arterial PGs and the capacity of plasma to remove cholesterol from extrahepatic cells (CEC)
Plasma cholesterol efflux capacity (CEC) by scavenger receptor class B type I (SR-BI) pathway was higher in summer than in winter, but this difference was lost when we evaluated the CEC using Apolipoprotein B (apoB)-depleted serum (Fig. 5D)
We believe that our results provide for the first time a mechanistic explanation that can contribute to the observed resistance to early atherogenesis of freeranging brown bears, despite their high circulating levels of cholesterol and TG, especially during chromatogram for each group ± standard error of the mean

Summary

Introduction

Plasma lipids circulate as lipoproteins with densities similar to those of human VLDL, LDL, and HDL [2,3,4,5]. We report on the lipoprotein composition and two functional properties that appear to modulate early atherogenesis in humans and preclinical mammalian models: the association of LDL with arterial PGs and the capacity of plasma to remove cholesterol from extrahepatic cells (CEC).

Results

Conclusion