Lipid-modified proteins as biomarkers for cardiovascular disease: a review.
Lipid-modified proteins are classified based on the identity of the attached lipid, a post- or co-translational modification required for their biological function. At least five different lipid modifications of cysteines, glycines and other residues on the COOH- and NH(2)-terminal domains have been described. Cysteine residues may be modified by the addition of a 16-carbon saturated fatty acyl group by a labile thioester bond (palmitoylation) or by prenylation processes that catalyze the formation of thioether bond with mevalonate derived isoprenoids, farnesol and geranylgeraniol. The NH(2)-terminal glycine residues may undergo a quite distinct process involving the formation of an amide bond with a 14-carbon saturated acyl group (myristoylation), while glycine residues in the COOH-terminal may be covalently attached with a cholesterol moiety by an ester bond. Finally, cell surface proteins can be anchored to the membrane through the addition of glycosylphosphatidylinositol moiety. Several lines of evidence suggest that lipid-modified proteins are directly involved in different steps of the development of lesions of atherosclerosis, from leukocyte recruitment to plaque rupture, and their expression or lipid modification are likely altered during atherogenesis. This review will briefly summarize the different enzymatic pathways of lipid modification and propose a series of lipid-modified proteins that can be used as biomarkers for cardiovascular disease.
Ferri
N
N
Department of Pharmacological Sciences, University of Milan, Milan, Italy.
Paoletti
R
R
Corsini
A
A
D000217:Acyltransferases / Q000378:metabolism; D001161:Arteriosclerosis / Q000503:physiopathology; D015415:Biomarkers; D002318:Cardiovascular Diseases / Q000175:diagnosis* / Q000188:drug therapy; D002784:Cholesterol / Q000378:metabolism; D003545:Cysteine / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D008565:Membrane Proteins / Q000378:metabolism*; D019814:Myristic Acid / Q000378:metabolism; D019308:Palmitic Acid / Q000378:metabolism; D017368:Protein Prenylation; D011499:Protein Processing, Post-Translational; D018631:ras Proteins / Q000378:metabolism
D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008565:Membrane Proteins; D019814:Myristic Acid; D019308:Palmitic Acid; D002784:Cholesterol; D000217:Acyltransferases; D018631:ras Proteins; D003545:Cysteine