Globular domain of adiponectin: promising target molecule for detection of atherosclerotic lesions

Abstract

Gunter Almer1, Matthias Saba-Lepek2, Samih Haj-Yahya1, Eva Rohde3, Dirk Strunk4, Eleonore Fröhlich5, Ruth Prassl2, Harald Mangge11Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, 2Institute of Biophysics and Nanosystems Research, Austrian Academy of Science, 3University Clinic of Blood Group Serology and Transfusion Medicine, 4University Clinic of Hematology, 5Center for Medical Research, Medical University of Graz, Graz, AustriaBackground: Adiponectin, an adipocyte-specific plasma protein, has been shown to accumulate in injured endothelial cells during development of atherosclerotic lesions. In this study, we investigated the potential of different adiponectin subfractions with special emphasis on globular adiponectin (gAd) to recognize and visualize atherosclerotic lesions.Methods: Recombinant mouse gAd and subfractions of full-length adiponectin (ie, trimeric, hexameric, and oligomeric forms) were fluorescence-labeled. Aortas of wild-type and apoprotein E-deficient mice fed a high cholesterol diet were dissected and incubated with the labeled biomarkers. Imaging was performed using confocal laser scanning microscopy.Results: Confocal laser scanning microscopic images showed that gAd binds more strongly to atherosclerotic plaques than full-length adiponectin subfractions. Further, we showed that gAd accumulates preferentially in endothelial cells and the fibrous cap area of plaques. Here we demonstrate for the first time that gAd recognizes atherosclerotic plaques on aortic sections of apoprotein E-deficient mice.Conclusion: These results suggest that gAd, in addition to its physiological properties, is also suitable as a target molecule for prospective diagnostic strategies in imaging atherosclerotic lesions.Keywords: adiponectin subfractions, atherosclerosis, fibrous cap, globular adiponectin, vascular imaging