Effect of LDL concentration polarization on the uptake of LDL by human endothelial cells and smooth muscle cells co-cultured

Abstract

To substantiate our hypothesis that concentration polarization of low-density lipoprotein (LDL) plays an important role in the localization of atherogenesis, we investigated the effects of wall shear stress and water filtration rate (or perfusion pressure) on the luminal surface LDL concentration (c w ) and the LDL uptake by human vascular endothelial cells and smooth muscle cells co-cultured on a permeable membrane using a parallel-plate flow chamber technique and a flow cytometry method. The results indicated that the uptake of fluorescent labeled LDL (DiI-LDL) by the co-cultured cells was positively correlated with c w in a non-linear fashion. When c w was low, the uptake increased very sharply with increasing c w . Then the increase became gradual and the uptake was seemingly leveled out when c w reached beyond 160 mg/ml. The present study therefore has provided further experimental evidence that concentration polarization may occur in the arterial system and have a positive correlation with the uptake of LDLs by the arterial wall, which gives support to our hypothesis regarding the localization of atherogenesis.

In vitro and in vivo investigations on the effects of low-density lipoprotein concentration polarization and haemodynamics on atherosclerotic localization in rabbit and zebrafish

“…Lipoprotein concentration polarization and flow field changes appear to lead to the alteration of atherogenic lipid transportation across the arterial luminal surface, causing vascular diseases such as lipoprotein deposition, blood platelet accumulation and intima thickening. Previous in vitro studies have shown that LDL concentration polarization exists in the vascular system [17][18][19][20][33][34][35][36]. In our study, the transparent segment of the rabbit carotid artery was vertically scanned along the z-axis using the computed tomography scanning capability of LSCM.…”

Effect of oxidized low-density lipoprotein concentration polarization on human smooth muscle cells' proliferation, cycle, apoptosis and oxidized low-density lipoprotein uptake

“…Ox-LDL is believed to play a key role in cellular dysfunction, as well as cholesterol accumulation and subsequent foam-cell transformation in macrophages and SMCs [12][13][14][15][16][17][18][19][20][21][22][23][24]. Because the endothelium of the artery displays low permeability to plasma proteins, it has been suggested that the filtration flow across the artery wall may cause concentration polarization of LDLs with the LDLs increasing in concentration from bulk value towards interface within the arterial system [8].…”

“…The same experimental perfusion system as the one described previously by Ding et al [20] was used in the present study ( figure 1). It consisted of a head tank, a downstream collecting reservoir, a modified parallelplate flow chamber with a height of 0.5 Â 10 23 m, a peristaltic flow pump to circulate the perfusion fluid (DMEM) and a blender of air and CO 2 with a constant temperature (378C + 18C).…”

Biomechanical regulation of vascular smooth muscle cell functions: from in vitro to in vivo understanding

“…With increasing LDL concentration, shear stress increases LDL uptake by human ECs when co-cultured with VSMCs [140]. Shear stress inhibits VSMC-induced inflammatory gene expression in ECs [141].…”