Lipid mediators that modulate the extracellular matrix structure and function in vascular cells.

Treatment with moderate levels of albumin-bound, nonesterified fatty acids (NEFA) induce important alterations of the structure and functionality of proteoglycans secreted by endothelial cells and arterial smooth muscle cells. In endothelial cell monolayers, the reduction on relative amount and sulfation of heparan sulfate proteoglycans is associated with an increased permeability to albumin. In smooth muscle cells, NEFA-albumin complex increased the expression of the genes for the core proteins of the proteoglycans syndecan, decorin and perlecan. This effect appears mediated by peroxisome proliferator-activated receptor gamma (PPARg). The matrix produced by the cells treated with NEFA-albumin had a higher affinity with low-density lipoproteins (LDLs). We speculate about the possibility that under dyslipidemias associated with increased exposure of vascular cells to NEFA, like in type 2 diabetes, similar alterations may contribute to associated macrovascular and microvascular complications.