P10.05 REDUCED MOLECULAR FLEXIBILITY IN THE LARGE ARTERIES OF DIABETIC RATS

DOI

10.1016/j.artres.2009.10.136How to use a DOI?

Abstract

In Type 1 and 2 diabetes tissue stiffening is evident from measurements of the gross mechanical properties of the vasculature. In general, pathological glycosylation of extracellular matrix proteins may play an important role in increasing stiffness in diabetic patients. However, the effects of diabetes on individual elastic fibre components remain poorly defined.

Fibrillin microfibrils, a key elastic fibre component, have a ‘beads-on-a-string’ structure with a periodicity of approximately 56nm. We tested for possible disruption due to diabetes in fibrillin microfibrils isolated from rat aorta. Diabetes was induced in 250g adult Wistar rats by streptozotocin (STZ) injection (55mg/kg) and were sacrificed 8 weeks later along with age-matched controls. At sacrifice, the STZ-treated rats had severe hyperglycaemia (+/− 28mmol/l). Fibrillin microfibrils were isolated and purified by well-established bacterial collagenase digestion and size-exclusion chromatography prior to imaging with atomic force microscopy.

Initial experiments show that fibrillin microfibril periodicity is reduced following STZ treatment; 52.0 +/− 0.4nm (STZ) vs 56.9 +/− 0.4nm (Control), n=600 periodicity measurements, 2 animals per group), (p<0.01). In young, healthy tissues the structure of fibrillin microfibrils is stabilised by both intra- and inter-chain disulphide bonds and by transglutaminase cross-links which permit reversible extension in vivo. These observations suggest that the formation of pathological cross-links may limit microfibril elasticity and hence play an important role in increasing the stiffness of the diabetic vasculature.

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TY  - JOUR
AU  - R. Akhtar
AU  - N. Gardiner
AU  - J.K. Cruickshank
AU  - B. Derby
AU  - M.J. Sherratt
PY  - 2009
DA  - 2009/12/03
TI  - P10.05 REDUCED MOLECULAR FLEXIBILITY IN THE LARGE ARTERIES OF DIABETIC RATS
JO  - Artery Research
SP  - 192
EP  - 192
VL  - 3
IS  - 4
SN  - 1876-4401
UR  - https://doi.org/10.1016/j.artres.2009.10.136
DO  - 10.1016/j.artres.2009.10.136
ID  - Akhtar2009
ER  -