Paraoxonase-3 is depleted from the high-density lipoproteins of autoimmune disease patients with subclinical atherosclerosis.
Patients with autoimmune diseases have a significantly increased risk of developing cardiovascular disease. In disease, high-density lipoprotein (HDL) particles lose their anti-inflammatory and antioxidant properties and become dysfunctional. The purpose of this study was to test the hypothesis that alterations in the HDL proteomic profile are associated with subclinical atherosclerosis and HDL dysfunction in patients with autoimmune diseases such as systemic lupus erythematosus (SLE) and type 1 diabetes. Targeted proteomics was used to quantify the relative abundance of 18 proteins in HDL from SLE patients with and without atherosclerotic plaque detectable by carotid ultrasound. Changes in the proteomic profile were compared against the in vitro ability of HDL to protect against lipid oxidation. The same proteins were quantified in HDL from patients with type 1 diabetes with or without coronary artery calcification as determined by computed tomography. In each population, paraoxonase-3 (PON3), a potent antioxidant protein, was depleted from the HDL of patients with subclinical atherosclerosis. PON3 expression in HDL was positively correlated with HDL antioxidant function. These results suggest that PON3 may be an important protein in preventing atherosclerosis and highlight the importance of antioxidant proteins in the prevention of atherosclerosis in vivo.
Judit
J
Marsillach
Jessica O
JO
Becker
Tomas
T
Vaisar
§Department of Medicine (Division of Rheumatology), University of California Los Angeles, 1000 Veteran Avenue 32-59, Los Angeles, California 90095, United States.
Bevra H
BH
Hahn
John D
JD
Brunzell
⊥Department of Genome Sciences, University of Washington, 3720 Fifteenth Avenue Northeast, Seattle, Washington 98195, United States.
Clement E
CE
Furlong
¶Kidney Research Institute, University of Washington, 325 Ninth Avenue, Seattle, Washington 98104, United States.
Ian H
IH
de Boer
§Department of Medicine (Division of Rheumatology), University of California Los Angeles, 1000 Veteran Avenue 32-59, Los Angeles, California 90095, United States.
Maureen A
MA
McMahon
¶Kidney Research Institute, University of Washington, 325 Ninth Avenue, Seattle, Washington 98104, United States.
Andrew N
AN
Hoofnagle
D000328:Adult; D000975:Antioxidants / Q000302:isolation & purification / Q000378:metabolism; D043303:Aryldialkylphosphatase / Q000172:deficiency / Q000235:genetics* / Q000302:isolation & purification; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000276:immunology / Q000473:pathology; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000175:diagnosis* / Q000201:enzymology / Q000276:immunology; D005260:Female; D015870:Gene Expression; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood / Q000737:chemistry*; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000175:diagnosis* / Q000201:enzymology / Q000276:immunology; D008297:Male; D008875:Middle Aged; D058226:Plaque, Atherosclerotic / Q000150:complications / Q000175:diagnosis* / Q000201:enzymology / Q000276:immunology; D040901:Proteomics; D053719:Tandem Mass Spectrometry; D014463:Ultrasonography
D000975:Antioxidants; D008075:Lipoproteins, HDL; D043303:Aryldialkylphosphatase; C113656:PON3 protein, human
carotid plaque; coronary artery calcification; dysfunctional; high-density lipoproteins; mass spectrometry; paraoxonase-3; pro-inflammatory; systemic lupus erythematosus; type 1 diabetes