Localized micro- and nano-scale remodelling in the diabetic aortaCitation formats

  • External authors:
  • R. Akhtar
  • J. K. Cruickshank
  • X. Zhao
  • L. A. Walton
  • S. D. Barrett
  • H. K. Graham

Standard

Localized micro- and nano-scale remodelling in the diabetic aorta. / Akhtar, R.; Cruickshank, J. K.; Zhao, X.; Walton, L. A.; Gardiner, N. J.; Barrett, S. D.; Graham, H. K.; Derby, B.; Sherratt, M. J.

In: Acta Biomaterialia, 24.02.2014.

Research output: Contribution to journalArticlepeer-review

Harvard

Akhtar, R, Cruickshank, JK, Zhao, X, Walton, LA, Gardiner, NJ, Barrett, SD, Graham, HK, Derby, B & Sherratt, MJ 2014, 'Localized micro- and nano-scale remodelling in the diabetic aorta', Acta Biomaterialia. https://doi.org/10.1016/j.actbio.2014.07.001

APA

Akhtar, R., Cruickshank, J. K., Zhao, X., Walton, L. A., Gardiner, N. J., Barrett, S. D., Graham, H. K., Derby, B., & Sherratt, M. J. (2014). Localized micro- and nano-scale remodelling in the diabetic aorta. Acta Biomaterialia. https://doi.org/10.1016/j.actbio.2014.07.001

Vancouver

Akhtar R, Cruickshank JK, Zhao X, Walton LA, Gardiner NJ, Barrett SD et al. Localized micro- and nano-scale remodelling in the diabetic aorta. Acta Biomaterialia. 2014 Feb 24. https://doi.org/10.1016/j.actbio.2014.07.001

Author

Akhtar, R. ; Cruickshank, J. K. ; Zhao, X. ; Walton, L. A. ; Gardiner, N. J. ; Barrett, S. D. ; Graham, H. K. ; Derby, B. ; Sherratt, M. J. / Localized micro- and nano-scale remodelling in the diabetic aorta. In: Acta Biomaterialia. 2014.

Bibtex

@article{2adef1f150594c24a4831435af3d09e4,
title = "Localized micro- and nano-scale remodelling in the diabetic aorta",
abstract = "Diabetes is strongly associated with cardiovascular disease, but the mechanisms, structural and biomechanical consequences of aberrant blood vessel remodelling remain poorly defined. Using an experimental (streptozotocin, STZ) rat model of diabetes, we hypothesized that diabetes enhances extracellular protease activity in the aorta and induces morphological, compositional and localized micromechanical tissue remodelling. We found that the medial aortic layer underwent significant thickening in diabetic animals but without significant changes in collagen or elastin (abundance). Scanning acoustic microscopy demonstrated that such tissue remodelling was associated with a significant decrease in acoustic wave speed (an indicator of reduced material stiffness) in the inter-lamellar spaces of the vessel wall. This index of decreased stiffness was also linked to increased extracellular protease activity (assessed by semi-quantitative in situ gelatin zymography). Such a proteolytically active environment may affect the macromolecular structure of long-lived extracellular matrix molecules. To test this hypothesis, we also characterized the effects of diabetes on the ultrastructure of an important elastic fibre component: the fibrillin microfibril. Using size exclusion chromatography and atomic force microscopy, we isolated and imaged microfibrils from both healthy and diabetic aortas. Microfibrils derived from diabetic tissues were fragmented, morphologically disrupted and weakened (as assessed following molecular combing). These structural and functional abnormalities were not replicated by in vitro glycation. Our data suggest that proteolysis may be a key driver of localized mechanical change in the inter-lamellar space of diabetic rat aortas and that structural proteins (such as fibrillin microfbrils) may be biomarkers of diabetes induced damage. {\textcopyright} 2014 Acta Materialia Inc.",
keywords = "Arterial stiffening, Extracellular matrix, Fibrillin microfibrils, Mechanical properties, Type 1 diabetes",
author = "R. Akhtar and Cruickshank, {J. K.} and X. Zhao and Walton, {L. A.} and Gardiner, {N. J.} and Barrett, {S. D.} and Graham, {H. K.} and B. Derby and Sherratt, {M. J.}",
year = "2014",
month = feb,
day = "24",
doi = "10.1016/j.actbio.2014.07.001",
language = "English",
journal = "Acta Biomaterialia",
issn = "1742-7061",
publisher = "Elsevier BV",

}

RIS

TY - JOUR

T1 - Localized micro- and nano-scale remodelling in the diabetic aorta

AU - Akhtar, R.

AU - Cruickshank, J. K.

AU - Zhao, X.

AU - Walton, L. A.

AU - Gardiner, N. J.

AU - Barrett, S. D.

AU - Graham, H. K.

AU - Derby, B.

AU - Sherratt, M. J.

PY - 2014/2/24

Y1 - 2014/2/24

N2 - Diabetes is strongly associated with cardiovascular disease, but the mechanisms, structural and biomechanical consequences of aberrant blood vessel remodelling remain poorly defined. Using an experimental (streptozotocin, STZ) rat model of diabetes, we hypothesized that diabetes enhances extracellular protease activity in the aorta and induces morphological, compositional and localized micromechanical tissue remodelling. We found that the medial aortic layer underwent significant thickening in diabetic animals but without significant changes in collagen or elastin (abundance). Scanning acoustic microscopy demonstrated that such tissue remodelling was associated with a significant decrease in acoustic wave speed (an indicator of reduced material stiffness) in the inter-lamellar spaces of the vessel wall. This index of decreased stiffness was also linked to increased extracellular protease activity (assessed by semi-quantitative in situ gelatin zymography). Such a proteolytically active environment may affect the macromolecular structure of long-lived extracellular matrix molecules. To test this hypothesis, we also characterized the effects of diabetes on the ultrastructure of an important elastic fibre component: the fibrillin microfibril. Using size exclusion chromatography and atomic force microscopy, we isolated and imaged microfibrils from both healthy and diabetic aortas. Microfibrils derived from diabetic tissues were fragmented, morphologically disrupted and weakened (as assessed following molecular combing). These structural and functional abnormalities were not replicated by in vitro glycation. Our data suggest that proteolysis may be a key driver of localized mechanical change in the inter-lamellar space of diabetic rat aortas and that structural proteins (such as fibrillin microfbrils) may be biomarkers of diabetes induced damage. © 2014 Acta Materialia Inc.

AB - Diabetes is strongly associated with cardiovascular disease, but the mechanisms, structural and biomechanical consequences of aberrant blood vessel remodelling remain poorly defined. Using an experimental (streptozotocin, STZ) rat model of diabetes, we hypothesized that diabetes enhances extracellular protease activity in the aorta and induces morphological, compositional and localized micromechanical tissue remodelling. We found that the medial aortic layer underwent significant thickening in diabetic animals but without significant changes in collagen or elastin (abundance). Scanning acoustic microscopy demonstrated that such tissue remodelling was associated with a significant decrease in acoustic wave speed (an indicator of reduced material stiffness) in the inter-lamellar spaces of the vessel wall. This index of decreased stiffness was also linked to increased extracellular protease activity (assessed by semi-quantitative in situ gelatin zymography). Such a proteolytically active environment may affect the macromolecular structure of long-lived extracellular matrix molecules. To test this hypothesis, we also characterized the effects of diabetes on the ultrastructure of an important elastic fibre component: the fibrillin microfibril. Using size exclusion chromatography and atomic force microscopy, we isolated and imaged microfibrils from both healthy and diabetic aortas. Microfibrils derived from diabetic tissues were fragmented, morphologically disrupted and weakened (as assessed following molecular combing). These structural and functional abnormalities were not replicated by in vitro glycation. Our data suggest that proteolysis may be a key driver of localized mechanical change in the inter-lamellar space of diabetic rat aortas and that structural proteins (such as fibrillin microfbrils) may be biomarkers of diabetes induced damage. © 2014 Acta Materialia Inc.

KW - Arterial stiffening

KW - Extracellular matrix

KW - Fibrillin microfibrils

KW - Mechanical properties

KW - Type 1 diabetes

U2 - 10.1016/j.actbio.2014.07.001

DO - 10.1016/j.actbio.2014.07.001

M3 - Article

C2 - 25014552

JO - Acta Biomaterialia

JF - Acta Biomaterialia

SN - 1742-7061

ER -