The Effect of Type 1 Diabetes on the Structure and Function of Fibrillin Microfibrils

Abstract

AbstractIn Type 1 and 2 diabetes tissue stiffening is evident from measurements of the gross mechanical properties of the vasculature. Elastic fibers play an important role in the mechanical function of vascular tissue, however, the effects of diabetes on individual elastic fiber components remains poorly defined. Fibrillin microfibrils, a key elastic fiber component, have a ‘beads-on-a-string’ structure with a periodicity of approximately 56 nm. We tested for possible disruption due to diabetes in fibrillin microfibrils isolated from rat aorta using an experimental model of Type 1 diabetes in rats. The isolated fibrillin microfibrils were imaged with atomic force microscopy (AFM) and image analysis techniques were used to characterise the microfibrils. Although there was no significant difference in mean microfibril length (control 23.2 repeats, SEM 6.2 repeats: diabetic 23.6 repeats, SEM 6.1 repeats: Mann Whitney U-test, p=0.391), mean periodicity was significantly reduced in microfibrils isolated from the diabetic rats (52.7 nm, SEM 0.4 nm) compared with age-matched controls (59.5 nm, SEM 0.4 nm) (p<0.001, Student's t-test). This study shows that diabetes leads to significant ultrastructural morphological changes in fibrillin microfibrils.