Selective microvascular dysfunction in mice lacking the gene encoding for desmin
Selective microvascular dysfunction in mice lacking the gene encoding for desmin
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DOI：
10.1096/fj.01-0505fje
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发表时间：
2001-11-01
期刊：
影响因子：
4.8
通讯作者：
Henrion, D
中科院分区：
文献类型：
--
作者：
Loufrani, L;Matrougui, K;Henrion, D
中间丝结蛋白在骨骼肌细胞和心肌细胞的完整性和收缩能力中起着关键作用。它的缺失或聚集会导致心肌病。在动脉中，结蛋白分布不均；如果没有结蛋白，也可能发生血管紊乱。我们研究了缺乏结蛋白(DES-/-)的小鼠的动脉内皮细胞和肌肉功能，并与对照组(DES+/+)进行了比较。在动脉造影术中，颈动脉和肠系膜阻力动脉在体外安装。Desmin仅定位于平滑肌细胞。在DES-/-小鼠的动脉中，压力诱导的(肌源性)张力没有变化，但激动剂诱导的阻力动脉的张力下降(大动脉没有变化)。在阻力动脉中，血流(切应力)和乙酰胆碱诱导的内皮依赖性以及非内皮依赖性的扩张也减少。据我们所知，这是第一次研究缺乏结蛋白的动脉的血管收缩和扩张功能。大动脉血管反应性正常，小阻力动脉血管反应性明显降低。因此，在血管平滑肌细胞和阻力动脉中，结蛋白是必需的，以有效控制血管张力，从而获得最佳的血流供应。在缺乏结蛋白的情况下发现的这种微血管缺陷可能在结蛋白相关疾病的肌病中起主要作用。
The intermediate filament desmin has a key role in the integrity and contractility of skeletal and cardiac myocytes. Its absence or aggregation leads to cardiomyopathies. In arteries desmin is distributed heterogeneously; vascular disorders might also occur in its absence. We studied endothelial and muscular functions in arteries from mice lacking desmin (des-/-), compared with control (des+/+). Carotid and mesenteric resistance arteries were mounted in vitro in arteriographs. Desmin was located exclusively in smooth muscle cells. In arteries from des-/- mice, pressure-induced (myogenic) tone was unchanged, but agonist-induced tone decreased in resistance arteries (no change in large arteries). Flow (shear stress)- and acetylcholine-induced, endothelium-dependent dilation, as well as endothelium-independent dilation, were also decreased in resistance arteries.To our knowledge, this is the first study of vascular contractile and dilatory functions in arteries lacking desmin. Although vascular reactivity was normal in large arteries, it decreased strongly in small resistance arteries. Thus, desmin is required in vascular smooth muscle cells and in resistance arteries, for efficient control of vascular tone and consequently for an optimal blood flow supply. This microvascular defect found in the absence of desmin might play a major role in myopathies seen in desmin-related diseases.