Localized micro- and nano-scale remodelling in the diabetic aorta.
Localized micro- and nano-scale remodelling in the diabetic aorta.
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DOI：
10.1016/j.actbio.2014.07.001
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发表时间：
2014-11
影响因子：
9.7
通讯作者：
Sherratt, M. J.
中科院分区：
文献类型：
--
作者：
Akhtar, R.;Cruickshank, J. K.;Zhao, X.;Walton, L. A.;Gardiner, N. J.;Barrett, S. D.;Graham, H. K.;Derby, B.;Sherratt, M. J.
关键词：
糖尿病与心血管疾病密切相关，但异常血管重塑的机制、结构和生物力学后果仍不清楚。使用实验性（链脲佐菌素，STZ）糖尿病大鼠模型，我们假设糖尿病增强主动脉中的细胞外蛋白酶活性，并诱导形态、成分和局部微机械组织重塑。我们发现糖尿病动物的内侧主动脉层显着增厚，但胶原蛋白或弹性蛋白（丰度）没有显着变化。扫描声学显微镜表明，这种组织重塑与血管壁层间空间中声波速度（材料刚度降低的指标）的显着降低有关。这种硬度降低的指数也与细胞外蛋白酶活性的增加有关（通过半定量原位明胶酶谱法评估）。这种蛋白水解活性环境可能会影响长寿命细胞外基质分子的大分子结构。为了检验这一假设，我们还表征了糖尿病对重要弹性纤维成分（原纤维蛋白微原纤维）超微结构的影响。使用尺寸排阻色谱和原子力显微镜，我们从健康和糖尿病主动脉中分离出微纤维并对其进行成像。来自糖尿病组织的微纤维被破碎、形态被破坏和削弱（根据分子梳理后的评估）。这些结构和功能异常不能通过体外糖化来复制。我们的数据表明，蛋白水解可能是糖尿病大鼠主动脉板层间局部机械变化的关键驱动因素，而结构蛋白（如原纤维蛋白微纤维）可能是糖尿病引起的损伤的生物标志物。
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.
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影响因子：
7.7
作者：
Karamoysoyli, Eugenia;Burnand, Rebecca C.;Gardiner, Natalie J.
通讯作者：
Gardiner, Natalie J.
影响因子：
8.6
作者：
BENSIMON, D;SIMON, AJ;BENSIMON, A
通讯作者：
BENSIMON, A
影响因子：
5.3
作者：
Faia, KL;Davis, WP;Foxall, TL
通讯作者：
Foxall, TL
DOI：
10.1530/acta.0.0980432
发表时间：
1981-01-01
期刊：
ACTA ENDOCRINOLOGICA
影响因子：
--
作者：
ANDREASSEN, TT;SEYERHANSEN, K;OXLUND, H
通讯作者：
OXLUND, H
影响因子：
5.3
作者：
Booms, P;Pregla, R;Robinson, PN
通讯作者：
Robinson, PN