Fatty acids cause alterations of human arterial smooth muscle cell proteoglycans that increase the affinity for low-density lipoprotein.

• 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 micromol/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 PPARgamma agonist rosiglitazone (10 micromol/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.

Nyckelord

Arteries

cytology

Atherosclerosis

metabolism

Cells

Cultured

Dyslipidemias

metabolism

Glycosyltransferases

metabolism

Humans

Hypoglycemic Agents

pharmacology

Insulin

pharmacology

Lectins

C-Type

genetics

metabolism

Linoleic Acid

pharmacology

Lipoproteins

LDL

metabolism

Muscle

Smooth

Vascular

cytology

drug effects

metabolism

Palmitates

pharmacology

Proteochondroitin Sulfates

genetics

metabolism

Proteoglycans

genetics

metabolism

RNA

Messenger

metabolism

Sulfates

metabolism

Sulfotransferases

metabolism

Triglycerides

metabolism

Versicans

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)