两种实验性非高血压模型中腹主动脉僵硬度增加及细胞与基质相互作用：长期化学性交感神经切除和去窦神经大鼠
Increased stiffness and cell-matrix interactions of abdominal aorta in two experimental nonhypertensive models: long-term chemically sympathectomized and sinoaortic denervated rats.
作者信息
Bouissou Camille, Lacolley Patrick, Dabire Hubert, Safar Michel E, Gabella Giorgio, Duchatelle Véronique, Challande Pascal, Bezie Yvonnick
机构信息
aINSERM, U955, Créteil bINSERM, U1116, Nancy cDiagnosis Center and Université René Descartes, Hôtel-Dieu Hospital, UFR Médecine, Paris, France dDepartment of Anatomy and Developmental Biology, University College London, London, UK eDepartment of Pathology, Groupe Hospitalier Paris Saint-Joseph fUPMC Univ Paris 06 gCNRS UMR 7190 hDepartment of Pharmacy, Groupe Hospitalier Paris Saint-Joseph, Paris, France *P.C. and Y.B. contributed equally to the writing of the article.
出版信息
J Hypertens. 2014 Mar;32(3):652-8. doi: 10.1097/HJH.0000000000000073.
RATIONALE
Sinoaortic denervated (SAD) and chemically sympathectomized (SNX) rats are characterized by a decrease in arterial distensibility without hypertension and would, thus, be relevant for analyzing arterial wall stiffening independently of blood pressure level. The fibronectin network, which plays a pivotal role in cell-matrix interactions, is a major determinant of arterial stiffness. We hypothesized that in SAD and SNX rats, arterial stiffness is increased, due to alterations of cell-matrix anchoring leading to spatial reorganization of the extracellular matrix.
METHODS
The intrinsic elastic properties of the arterial wall were evaluated in vivo by the relationship between incremental elastic modulus determined by echotracking and circumferential wall stress. The changes of cell-extracellular matrix links in the abdominal aorta were evaluated by studying fibronectin, vascular integrin receptors, and ultrastructural features of the aorta by immunochemistry.
RESULTS
In both experimental conditions, wall stiffness increased, associated with different modifications of cell-extracellular matrix adhesion. In SAD rats, increased media cross-sectional area was coupled with an increase of muscle cell attachments to its extracellular matrix via fibronectin and its α5-β1 integrin. In SNX rats, reduced media cross-sectional area was associated with upregulation of αv-β3 integrin and more extensive connections between dense bands and elastic fibers despite the disruption of the elastic lamellae.
CONCLUSION
In aorta of SNX and SAD rats, a similar arterial stiffness is associated to different structural alterations. An increase in αvβ3 or α5β1 integrins together with the already reported increase in the proportion of less distensible (collagen) to more distensible (elastin) components in both models contributes to remodeling and stiffening of the abdominal aorta.
理论依据
去窦弓神经支配（SAD）和化学性交感神经切除（SNX）的大鼠的特征是动脉扩张性降低但无高血压，因此，对于独立于血压水平分析动脉壁硬化具有重要意义。纤连蛋白网络在细胞与基质相互作用中起关键作用，是动脉僵硬度的主要决定因素。我们假设，在SAD和SNX大鼠中，由于细胞与基质锚定的改变导致细胞外基质的空间重组，动脉僵硬度增加。
方法
通过超声跟踪测定的增量弹性模量与周向壁应力之间的关系，在体内评估动脉壁的固有弹性特性。通过免疫化学研究腹主动脉中纤连蛋白、血管整合素受体和主动脉的超微结构特征，评估细胞与细胞外基质连接的变化。
结果
在两种实验条件下，壁僵硬度均增加，伴有细胞与细胞外基质黏附的不同改变。在SAD大鼠中，中膜横截面积增加，同时肌细胞通过纤连蛋白及其α5-β1整合素与其细胞外基质的附着增加。在SNX大鼠中，中膜横截面积减小，与αv-β3整合素上调以及致密带与弹性纤维之间更广泛的连接有关，尽管弹性板遭到破坏。
结论
在SNX和SAD大鼠的主动脉中，相似的动脉僵硬度与不同的结构改变有关。在这两种模型中，αvβ3或α5β1整合素的增加，以及已报道的较不易扩张（胶原蛋白）与较易扩张（弹性蛋白）成分比例的增加，都有助于腹主动脉的重塑和硬化。
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