L-ascorbic acid stimulates expression of smooth muscle-specific markers in smooth muscle cells both in vitro and in vivo
L-ascorbic acid stimulates expression of smooth muscle-specific markers in smooth muscle cells both in vitro and in vivo
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DOI：
10.1097/00005344-200312000-00008
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发表时间：
2003-12-01
影响因子：
3
通讯作者：
Matsuda, Y
中科院分区：
文献类型：
--
作者：
Arakawa, E;Hasegawa, K;Matsuda, Y
血管平滑肌细胞(VSMCs)的去分化在动脉粥样硬化和血管成形术后再狭窄的进展中起着关键作用。因此，刺激平滑肌细胞分化的因子对这些疾病的治疗应该是有用的。此前，我们发现L-抗坏血酸(L-抗坏血酸)可诱导多能骨髓基质细胞系Tbr-B中平滑肌特异基因的表达。这一发现提示，L-天冬氨酸具有促进血管细胞分化的作用。在本研究中，我们研究了L-天冬氨酸及其衍生物在体外和体内对血管平滑肌细胞分化状态的影响。L及其长效衍生物以剂量依赖的方式刺激培养的大鼠VSMC产生肌球蛋白重链1(SM1)和钙蛋白I，并维持2周以上。更有甚者。与单纯给药组相比，球囊损伤大鼠口服3g/kg L-ASC可诱导损伤动脉SM1和Calponin 1的表达增加。这些数据显示了L-天冬氨酸及其长效衍生物的新的生物学活性，如刺激血管平滑肌细胞分化。此外，这些化合物可能成为分析血管平滑肌细胞分化和治疗血管疾病的有用工具。
The dedifferentiation of vascular smooth muscle cells (VSMCs) plays a critical role in the progression of atherosclerosis and restenosis after angioplasty. Thus, factors that stimulate smooth muscle cell differentiation should be useful for therapy for these diseases. Previously, we found that L-ascorbic acid (L-Asc) induces the expression of smooth muscle-specific genes in a pluripotent bone marrow stromal cell line, TBR-B. This finding suggests that L-Asc stimulates the differentiation of smooth muscle cells. In the present study, we investigated the effects Of L-Asc and its derivatives on the differentiation state of VSMCs in vitro and in Vivo. L-Asc and its long-lasting derivatives stimulated the production of smooth muscle-specific myosin heavy chain-1 (SM1) and calponin I in a dose-dependent manner in rat cultured VSMCs, and the elevated production of SM1 and calponin 1 was maintained for at least 2 weeks. Moreover. oral administration of 3 g/kg of L-Asc to the balloon-injured rats induced a higher expression of SM1 and calponin 1 in the injured arteries compared with that from administration of the delivery vehicle alone. These data demonstrated new biologic activity, such as the stimulation of VSMC differentiation, of L-Asc and its long-lasting derivatives. In addition, these compounds may serve as useful tools for analysis of the differentiation of VSMCs and for therapy for vascular diseases.