HOT TOPIC Although cardio-vascular disease is increased in both type 1 and type 2 diabetes, the exact reason for this augmented risk is not known.

Terje Lund

A new study from Oslo Diabetes Research Centre

Advanced glycation end-products (AGEs)  are considered to be a major pathogenic factor for diabetic vascular complications. AGEs are modifications of proteins by glucose or intracellular intermediates of glucoseThe levels of AGEs are increased in diabetic patients. In a new study, the research Centre  has studied the presence of the major AGE methylglyoxal (MGO)-derived hydroimidazolone in human aorta and carotid arteries, using immunohistochemistry (IHC), western blotting and mass spectrometry. By IHC, MGO-derived modifications were detected mainly associated with cells in intimal thickenings and cells in microvessels in adventitia. In type V lesions MGO-derived AGE was also present, extracellular in the necrotic core and in cells at the border of the core. The highest degree of modification was probably associated with cell nuclei. By western blotting and mass spectrometry fibrin(ogen), the cytoskeleton-associated protein moesin and the nuclear proteins lamin A and C were identified as putative main targets for MGO-derived modification. LC-MS/MS studies of fibrin(ogen) modified in vitro with low concentrations of MGO identified the sites that were most prone to modification. These results indicate that AGE modifications occur preferentially on specific proteins. The modification of these proteins may play a role in vascular dysfunction and development of atherosclerosis in diabetes.

Fibrin(ogen) may be an important target for methylglyoxal-derived AGE modification in elastic arteries of humans

Terje Lund, Ph.D,Department of Endocrinology – Section Hormone Laboratory, Oslo University Hospital, Norway

Aud Svindland,Department of Pathology, Oslo University Hospital, Norway

Milaim Pepaj,Department of Endocrinology – Section Hormone Laboratory, Oslo University Hospital, Norway

Aase-Brith Jensen,Department of Endocrinology – Section Hormone Laboratory, Oslo University Hospital, Norway

Jens P Berg,Department of Medical Biochemistry, Oslo University Hospital, Norway

Bente Kilhovd,Department of Endocrinology, Oslo University Hospital, Norway

Kristian F Hanssen,Department of Endocrinology, Oslo University Hospital; Institute of Clinical Medicine, University of Oslo, Norway

Diabetes and Vascular Disease Research August 15, 2011 In Press