Fatty acid-induced atherogenic changes in extracellular matrix proteoglycans.
OBJECTIVE
Nonesterified fatty acids change the expression and properties of the extracellular matrix proteoglycans of arterial and hepatic cells. We review how this may contribute to arterial disease in insulin resistance and type 2 diabetes.


RESULTS
Elevated nonesterified fatty acids characterize the dyslipidemia of insulin resistance and type 2 diabetes. In hepatocytes high levels of fatty acids cause changes in proteoglycans leading to a matrix with decreased affinity for VLDL remnants. Furthermore, liver proteoglycans from insulin resistant hyperlipidemic Zucker rats showed alterations also associated with decreased remnant affinity. In arterial smooth muscle cells overexposure to fatty acids augmented expression of matrix proteoglycans for which LDL showed increased affinity. Fatty acids appeared to compromise insulin signaling by protein kinase C activation. The observed fatty acid-induced changes in matrix proteoglycans in liver and arteries can be an important component of the atherogenicity of the dyslipidemia of insulin resistance and type 2 diabetes.


CONCLUSIONS
Overexposure to fatty acids can contribute to generate a remnant-rich dyslipidemia and to precondition the arterial intima for lipoprotein deposition via changes in expression of matrix proteoglycans. Normalizing fatty acid should be a key target in treatment of the atherogenic dyslipidemia of insulin resistance.
Rodriguéz-Lee
Mariam
M
Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
Bondjers
Göran
G
Camejo
Germán
G
D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008954:Models, Biological; D011509:Proteoglycans / Q000378:metabolism*
D005227:Fatty Acids; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D011509:Proteoglycans