title: Beta2-microglobulin as a biomarker in peripheral arterial disease: proteomic profiling and clinical studies.
abstract: BACKGROUND
  Peripheral arterial disease (PAD) is common but commonly unrecognized. Improved recognition of PAD is needed. We used high-throughput proteomic profiling to find PAD-associated biomarkers.
  
  
  RESULTS
  Plasma was collected from PAD patients (ankle brachial index of <0.90; n=45) and subjects with risk factors but without PAD (n=43). Plasma was analyzed with surface-enhanced laser desorption/ionization time-of-flight mass spectrometry to quantify 1619 protein peaks. The peak intensity of a 12-kDa protein was higher in PAD patients. Western blot analyses and immunoaffinity studies confirmed that this protein was beta2-microglobulin (B2M). In a validation study, B2M was measured by ELISA in plasma in age- and gender-matched PAD (n=20) and non-PAD (n=20) subjects. Finally, we studied a larger cohort of subjects (n=237) referred for coronary angiography but without known PAD. Plasma B2M levels were higher in PAD patients than in non-PAD patients with coronary artery disease. Plasma B2M correlated with ankle brachial index and functional capacity. Independent predictors of PAD were diabetes mellitus, age, and the combination of B2M and C-reactive protein level.
  
  
  CONCLUSIONS
  In PAD patients, circulating B2M is elevated and correlates with the severity of disease independent of other risk factors. These findings might provide a needed biomarker for PAD and new insight into its pathophysiology. Further studies in other populations are needed to confirm the utility of measuring B2M in cardiovascular disease risk assessment.
authors.affiliation: Stanford University School of Medicine, Division of Cardiovascular Medicine, 300 Pasteur Dr, Falk Cardiovascular Research Center, Stanford, CA 94305-5406, USA.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Wilson
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Kimura
authors.forename: Randall K
authors.initials: RK
authors.lastname: Harada
authors.forename: Nandini
authors.initials: N
authors.lastname: Nair
authors.forename: Balasubramanian
authors.initials: B
authors.lastname: Narasimhan
authors.forename: Xiao-Ying
authors.initials: XY
authors.lastname: Meng
authors.forename: Fujun
authors.initials: F
authors.lastname: Zhang
authors.forename: Kendall R
authors.initials: KR
authors.lastname: Beck
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Olin
authors.forename: Eric T
authors.initials: ET
authors.lastname: Fung
authors.forename: John P
authors.initials: JP
authors.lastname: Cooke
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000097:blood / Q000150:complications; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D015331:Cohort Studies; D048909:Diabetes Complications / Q000097:blood; D005260:Female; D006801:Humans; D007511:Ischemia / Q000097:blood* / Q000209:etiology; D007866:Leg / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D016491:Peripheral Vascular Diseases / Q000097:blood* / Q000209:etiology; D011237:Predictive Value of Tests; D040081:Protein Array Analysis; D040901:Proteomics / Q000379:methods*; D015427:Reperfusion Injury / Q000097:blood; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D001613:beta 2-Microglobulin / Q000032:analysis*
chemical_list: D015415:Biomarkers; D001613:beta 2-Microglobulin; D002097:C-Reactive Protein