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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:130.)
© 2006 American Heart Association, Inc.

Vascular Biology

Fatty Acids Cause Alterations of Human Arterial Smooth Muscle Cell Proteoglycans That Increase the Affinity for Low-Density Lipoprotein

Mariam Rodríguez-Lee; Gunnel Östergren-Lundén; Boel Wallin; Jonatan Moses; Göran Bondjers; Germán Camejo

From the Wallenberg Laboratory for Cardiovascular Research (M.R-L., G.Ö-L., G.B., J.M., G.C.), Sahlgrenska Academy at Göteborg University, Gothenburg, and AstraZeneca Discovery (B.W., G.C.), Mölndal, Sweden.

Correspondence to Göran Bondjers, Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska Academy at Göteborg University, 413 45 Gothenburg, Sweden. E-mail Goran.bondjers{at}wlab.gu.se

Objective— The dyslipidemia of insulin resistance, with high levels of albumin-bound fatty acids, is a strong cardiovascular disease risk. Human arterial smooth muscle cell (hASMC) matrix proteoglycans (PGs) contribute to the retention of apoB lipoproteins in the intima, a possible key step in atherogenesis. We investigated the effects of high NEFA levels on the PGs secreted by hASMCs and whether these effects might alter the PG affinity for low-density lipoprotein.

Methods and Results— hASMC exposed for 72 hours to high concentrations (800 µmol/L) of linoleate (LO) or palmitate upregulated the core protein mRNAs of the major PGs, as measured by quantitative PCR. Insulin (1 nmol/L) and the PPAR agonist rosiglitazone (10 µmol/L) blocked these effects. In addition, high LO increased the mRNA levels of enzymes required for glycosaminoglycan (GAG) synthesis. Exposure to NEFA increased the chondroitin sulfate:heparan sulfate ratio and the negative charge of the PGs. Because of these changes, the GAGs secreted by LO-treated cells had a higher affinity for human low-density lipoprotein than GAGs from control cells. Insulin and rosiglitazone inhibited this increase in affinity.

Conclusions— The response of hASMC to NEFA could induce extracellular matrix alterations favoring apoB lipoprotein deposition and atherogenesis.

We examined the effects of increased NEFA and insulin on the proteoglycans secreted by hASMC and whether these effects might affect LDL binding. The results indicate that increased fatty acids could induce qualitative and quantitative alterations of the intima extracellular matrix proteoglycans favoring LDL retention and possibly atherogenesis.

Key Words: proteoglycans • smooth muscle cells • LDL • fatty acids • insulin

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