Different involvement of extracellular matrix components in small and large arteries during chronic NO synthase inhibition
Different involvement of extracellular matrix components in small and large arteries during chronic NO synthase inhibition
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DOI：
10.1161/01.hyp.0000154680.44184.01
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发表时间：
2005-03-01
期刊：
影响因子：
8.3
通讯作者：
Moreau, P
中科院分区：
文献类型：
--
作者：
Bouvet, C;Gilbert, LA;Moreau, P
在原发性高血压中，导管动脉呈现肥厚性重构（增加的横截面积），而小动脉经历富营养性重构。基质金属蛋白酶（MMPs）和去粘附蛋白（例如腱生蛋白- C和血小板反应蛋白）的参与在大动脉重塑中已被相对较好地表征，但它们在小动脉重塑中的作用尚不清楚。在第1、3、7、14和28天，大鼠在其饮用水中接受N-ω-硝基- L-精氨酸甲酯（L-NAME; 50 mg/ kg/天）。用ELISA法测定动脉MMP- 2活性，用Western印迹法测定腱生蛋白C和血小板反应蛋白水平.为了确定MMP的参与，另外的L-NAME大鼠在第7、14和28天接受非选择性MMP抑制剂多西环素（30 mg/ kg/天）.在第1天，血压已经升高。肠系膜动脉和主动脉的中膜/管腔比逐渐增加，至28天时达到显著水平。然而，横截面积仅在主动脉中增加，证实了异质性重塑过程。在小动脉中，MMP- 2活性在治疗7天和14天后增加，并在28天时恢复至基线水平，而主动脉中的升高更为渐进但持续。在小动脉中血小板反应蛋白的水平超过MMP- 2的水平，而腱生蛋白- C的水平迅速下降并保持在对照值以下。多西环素钝化大动脉重塑，但对富营养化重塑的发展没有影响，尽管在此过程中MMP- 2活性升高。因此，与大动脉肥大性重塑（其中细胞去粘附和基质分解的贡献是明显的）相反，MMP在肥大性重塑中的贡献似乎不那么重要。
In essential hypertension, conduit arteries present hypertrophic remodeling ( increased cross- sectional area), whereas small arteries undergo eutrophic remodeling. The involvement of matrix metalloproteinases ( MMPs) and de- adhesion proteins, such as tenascin- C and thrombospondin, has been relatively well characterized in large artery remodeling, but their contribution is not known in small artery remodeling. Rats received N-omega- nitro- L- arginine methyl ester ( L- NAME; 50 mg/ kg per day) in their drinking water on days 1, 3, 7, 14, and 28. Arterial MMP- 2 activity was measured by ELISA, whereas levels of tenascin- C and thrombospondin were assessed by Western blotting. To determine the involvement of MMPs, additional L- NAME rats received the nonselective MMP inhibitor doxycycline ( 30 mg/ kg per day) on days 7, 14, and 28. Already, at day 1, pressure was elevated. Media/ lumen ratio of mesenteric arteries and the aorta increased gradually to reach significance at 28 days. However, the cross- sectional area increased only in the aorta, confirming the heterogeneous remodeling process. In small arteries, MMP- 2 activity increased after 7 and 14 days of treatment and returned to baseline at 28 days, whereas the elevation was more progressive but sustained in the aorta. The level of thrombospondin paralleled that of MMP- 2 in small arteries, whereas tenascin- C levels declined rapidly and stayed below control values. Doxycycline blunted large artery remodeling but had no influence on the development of eutrophic remodeling despite elevation of MMP- 2 activity in the process. Thus, in contrast to large artery hypertrophic remodeling, in which the contributions of cellular de- adhesion and matrix breakdown is manifest, the contribution of MMPs in eutrophic remodeling appears less crucial.