Temperature and hydrostatic pressure-dependent pathways of low-density lipoprotein transport across microvascular barrier

Abstract

To further investigate the chemical and physical nature of low-density lipoprotein (LDL) transport pathways across intact microvessels, the effect of changes in temperature and microvessel hydrostatic pressure were measured in individually perfused postcapillary vessels within frog mesenteric vascular beds. LDL microvessel transport was measured at two microvessel temperature ranges (18-21 degrees C and 4-6 degrees C) and compared with transport of fluorescein, a small solute. Also, LDL transport was measured at a series of hydrostatic pressures (3-20 cmH2O) at microvessel temperatures of 18-21 degrees C and 4-6 degrees C to determine whether LDL transport was coupled to water flow, which would be evidence for hydraulic pathways of solute transport across the microvascular barrier. Quantitative fluorescence microscopy was employed to determine apparent solute permeability coefficients (Ps) under the various temperature and hydrostatic pressure conditions studied. The ratio of Ps fluorescein 18-21 degrees C/4-6 degrees C [1.6 +/- 0.3 (SD)] indicated that fluorescein was freely diffusible across the microvascular barrier through water-filled pathways as transport was inversely proportional to temperature-dependent changes in viscosity. The larger ratio for LDL (Ps LDL 18-21/4-6 degrees C = 9.5 +/- 8.1) than for fluorescein cannot be explained by LDL transport through fixed hydraulic pathways alone and suggests additional or alternate LDL transport mechanisms. In addition, Ps LDL increased as microvessel hydrostatic pressure increased at microvessel temperatures of 18-21 degrees C but not at 4-6 degrees C. Coupling of LDL transport to water flow at the high microvessel temperature range, but not at the low range, indicated the presence of a hydraulic transport pathway that was effectively absent when the microvessel was cooled. These results demonstrated a highly temperature and hydrostatic pressure-dependent LDL pathway that is consistent with a dynamic porous extracellular or transcellular mechanism of LDL transport.