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.
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.
Authors: Roxana Martinez-Pinna; Coral Barbas; Luis Miguel Blanco-Colio; Jose Tunon; Priscila Ramos-Mozo; Juan Antonio Lopez; Olivier Meilhac; Jean-Baptiste Michel; Jesus Egido; José Luis Martin-Ventura Journal: Curr Atheroscler Rep Date: 2010-05 Impact factor: 5.113
Authors: Brian L Stauffer; Erich J Kushner; Ted Wulfman; Thomas Zeller; Rebecca Sobus; Christian M Westby Journal: Clin Transl Sci Date: 2008-12 Impact factor: 4.689
Authors: Kelly P Downing; Kevin T Nead; Yoko Kojima; Themistocles Assimes; Lars Maegdefessel; Thomas Quertermous; John P Cooke; Nicholas J Leeper Journal: Vasc Med Date: 2013-12-09 Impact factor: 3.239
Authors: F Vivanco; L R Padial; V M Darde; F de la Cuesta; G Alvarez-Llamas; Natacha Diaz-Prieto; M G Barderas Journal: Biomark Insights Date: 2008-03-12