Characterization of primary and restenotic atherosclerotic plaque from the superficial femoral artery: Potential role of Smad3 in regulation of SMC proliferation.
Characterization of primary and restenotic atherosclerotic plaque from the superficial femoral artery: Potential role of Smad3 in regulation of SMC proliferation.
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股动脉的原发性和再苯性动脉粥样硬化斑块的表征：SMAD3在调节SMC增殖中的潜在作用。
DOI：
10.1016/j.jvs.2008.11.096
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发表时间：
2009-05
影响因子：
4.3
通讯作者：
Kent, K. Craig
中科院分区：
文献类型：
--
作者：
Edlin, Rachel S.;Tsai, Shirling;Yamanouchi, Dai;Wang, Chunjie;Liu, Bo;Kent, K. Craig
描述和比较股浅动脉原发性和再狭窄病变，并分析TGF-β/Smad 3信号传导对外周动脉闭塞性疾病病理生理学的贡献。对从因原发性动脉粥样硬化或支架植入术后复发性疾病和/或既往血管成形术接受斑块切除术的患者股浅动脉中取出的标本进行免疫组织化学研究。免疫组化分析显示，再狭窄病变中平滑肌细胞（SMC）含量（α-肌动蛋白）和Smad 3表达显著升高，而原发性病变中白细胞（CD 45）和巨噬细胞（CD 68）显著升高。进一步的研究表明Smad 3与α-actin和PCNA共定位，提示Smad 3在再狭窄病变中观察到的增殖中的作用。为了证实Smad 3在SMC增殖中的作用，我们通过腺病毒介导的基因转移（AdSmad 3）上调Smad 3，并通过在人主动脉SMC中用siRNA转染来抑制Smad 3，用氚化胸苷评估增殖。Smad 3过表达增强细胞增殖，而抑制Smad 3则降低细胞增殖。细胞组成和细胞增殖的差异以及Smad 3仅在再狭窄疾病中表达的发现表明，TGF-β通过Smad 3信号传导可能在人类SMC增殖和再狭窄的病理生理学中发挥重要作用。
To characterize and compare primary and restenotic lesions of the superficial femoral artery and analyze the contribution of TGF-β/Smad3 signaling to the pathophysiology of peripheral artery occlusive disease. Immunohistochemical studies were performed on specimens retrieved from the superficial femoral artery of patients undergoing either atherectomy for primary atherosclerotic or recurrent disease after stenting and/or prior angioplasty. Immunohistochemical analysis revealed a significantly higher smooth muscle cell (SMC) content (α-actin) and expression of Smad3 in restenotic lesions while primary lesions contained significantly more leukocytes (CD45) and macrophages (CD68). Further studies demonstrated colocalization of Smad3 with α-actin and PCNA, suggesting a role for Smad3 in the proliferation observed in restenotic lesions. To confirm a role for Smad3 in SMC proliferation, we both upregulated Smad3 via adenoviral mediated gene transfer (AdSmad3) and inhibited Smad3 through transfection with siRNA in human aortic SMCs, assessing proliferation with tritiated thymidine. Overexpression of Smad3 enhanced whereas inhibition of Smad3 decreased cell proliferation. Differences in cellular composition and cell proliferation in conjunction with the finding that Smad3 is expressed exclusively in restenotic disease suggest that TGF-β, through Smad3 signaling, may play an essential role in SMC proliferation and the pathophysiology of restenosis in humans.
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影响因子：
20.1
作者：
Kobayashi, K;Yokote, K;Saito, Y
通讯作者：
Saito, Y
影响因子：
2.2
作者：
Hollenbeck, ST;Sakakibara, K;Kent, KC
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Kent, KC
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Skowasch, D;Jabs, A;Bauriedel, G
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Bauriedel, G
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15.9
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通讯作者：
WEIR, L
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作者：
Kearney, M;Pieczek, A;Isner, JM
通讯作者：
Isner, JM