Smooth Muscle Cells Influence Monocyte Response to LDL as well as Their Adhesion and Transmigration in a Coculture Model of the Arterial Wall

Abstract

We investigated the possible interference of smooth muscle cells with monocyte response to LDL as well as with their adhesion and transmigration in a coculture of porcine endothelial and smooth muscle cells. Lysophosphatidylcholine (LPC), a component of oxidized LDL (oxLDL), stimulated the adhesion of THP-1 cells to endothelial cells both in mono- and in coculture with smooth muscle cells. When THP-1 cells were incubated with endothelial cells in the presence of copper oxLDL, their adhesion was increased, but only in coculture. The addition of sodium nitroprusside (SNP) together with oxLDL markedly increased the adhesion of THP-1 cells in coculture. Close proximity between endothelial and smooth muscle cells was necessary to observe that effect. Furthermore, this increase in adhesion of THP-1 cells can, at least in part, be attributed to the augmented production of monocyte chemoattractant protein-1 (MCP-1) observed in coculture under the influence of oxLDL and SNP. The passage of THP-1 cells through the coculture was stimulated by MCP-1 and LPC. These results show that physical contacts or close proximity between endothelial and smooth muscle cells play a key role in the adhesion of monocytes and their infiltration into the intima in response to oxLDL.

A model for studying the effect of shear stress on interactions between vascular endothelial cells and smooth muscle cells

“…Since GRO-a and MCP-1 have been shown to be leukocyte adhesion factors on ECs (Weber et al, 1999), our results on GRO-a and MCP-1 gene induction in ECs cocultured with SMCs under static condition may explain the findings of and Kinard et al (2001) that leukocyte adhesion greatly increased in such cocultures. Though the mechanisms by which SMCs in coculture augment the GRO-a and MCP-1 gene expressions in ECs under static condition remain unclear, the importance of specific interaction between the cocultured ECs and SMCs in regulating EC gene expression was indicated by the lack of induction of these genes in ECs when ECs were cocultured with fibroblasts instead of SMCs.…”

Establishment of an interleukin-1β-induced inflammation-activated endothelial cell-smooth muscle cell-mononuclear cell co-culture model and evaluation of the anti-inflammatory effects of tanshinone IIA on atherosclerosis

“…These mediators can mutually affect functions through receptor mediation, myoendothelial bridges between ECs and SMCs, establishment of gap junctions and changes in the extracellular matrix components (14–16). The EC, SMC and mononuclear cell (MC) co-culture system, established on a polyethylene microporous membrane has revealed that the direct contact between ECs and SMCs serves a key function in MC adhesion and infiltration, and also accelerates the adhesion dynamics of THP-1 cells with ECs (17). MC infiltration, foam cell formation, the expression of interleukin (IL)-8 in SMCs and collagen deposition have been observed in the EC-SMC co-culture system, using fibrin gel as the scaffold (18).…”

Inhibitory effects of cariporide on LPC-induced expression of ICAM-1 and adhesion of monocytes to smooth muscle cells in vitro

“…The recruitment of monocytederived macrophages under endothelium hyperplasia and the migration of arterial SMC contribute to inflammation and the development of intimal hyperplasia during atherosclerosis. In addition to endothelial cells, vascular SMC also play an important role in the development and progress of atherosclerosis [9,19,20] . It is known that the damage of endothelium-dependent relaxation of blood vessels and the formation of the atherosclerotic plaque caused by hypercholesterolemia is related to circulating ox-LDL.…”