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. METHODS AND 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.
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Authors | Andrew M Wilson, Eiichiro Kimura, Randall K Harada, Nandini Nair, Balasubramanian Narasimhan, Xiao-Ying Meng, Fujun Zhang, Kendall R Beck, Jeffrey W Olin, Eric T Fung, John P Cooke |
Journal | Circulation
(Circulation)
Vol. 116
Issue 12
Pg. 1396-403
(Sep 18 2007)
ISSN: 1524-4539 [Electronic] United States |
PMID | 17724262
(Publication Type: Evaluation Study, Journal Article, Research Support, N.I.H., Extramural, Validation Study)
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Chemical References |
- Biomarkers
- beta 2-Microglobulin
- C-Reactive Protein
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Topics |
- Aged
- Aged, 80 and over
- Atherosclerosis
(blood, complications)
- Biomarkers
(blood)
- C-Reactive Protein
(analysis)
- Cohort Studies
- Diabetes Complications
(blood)
- Female
- Humans
- Ischemia
(blood, etiology)
- Leg
(blood supply)
- Male
- Middle Aged
- Peripheral Vascular Diseases
(blood, etiology)
- Predictive Value of Tests
- Protein Array Analysis
- Proteomics
(methods)
- Reperfusion Injury
(blood)
- Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
- beta 2-Microglobulin
(analysis)
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