C-type natriuretic peptide induces redifferentiation of vascular smooth muscle cells with accelerated reendothelialization
C-type natriuretic peptide induces redifferentiation of vascular smooth muscle cells with accelerated reendothelialization
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DOI：
10.1161/01.atv.21.6.930
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发表时间：
2001-06-01
影响因子：
8.7
通讯作者：
Nakao, K
中科院分区：
文献类型：
--
作者：
Doi, K;Ikeda, T;Nakao, K
我们最近报道，C型利钠肽（CNP）存在于血管内皮细胞，并作为血管型利钠肽。在本研究中，我们刺激cGMP级联在增殖平滑肌细胞（SMC），其中颗粒鸟苷酸环化酶-B，CNP的特异性受体，主要表达，通过使用腺病毒编码大鼠CNP cDNA（Ad.CNP）。在Ad. CNP处理的培养SMC中，CNP导致SMC生长抑制于G_1期，早期p21（CIP 1/WAF 1）表达增加，随后p16（INK 4a）表达上调。Ad，CNP处理的SMCs再表达高分化SMCs的分子标志物平滑肌肌球蛋白重链2（smooth muscle myosin heavy chain-2），Ad，CNP处理的SMCs也再表达特异性表达的鸟苷酸环化酶A（guanylate cyclase-A）。CNP在球囊损伤时在体内兔股动脉中过表达，显著抑制新生内膜形成。此外，平滑肌肌球蛋白重链-2的表达增强发生在残留的新生内膜。此外，在Ad. CNP感染组中观察到内皮细胞的早期再生。因此，在增殖的去分化的SMC中刺激cGMP级联可以诱导SMC的生长抑制和再分化，并加速再内皮化。
We recently reported that C-type natriuretic peptide (CNP) occurs in vascular endothelial cells and acts as a vascular-type natriuretic peptide. In the present study, we stimulated the cGMP cascade in proliferating smooth muscle cells (SMCs), in which particulate guanylate cyclase-B, the specific receptor for CNP, is predominantly expressed, by use of an adenovirus encoding rat CNP cDNA (Ad.CNP). In the Ad.CNP-treated cultured SMCs, CNP caused the growth inhibition of SMCs at G, phase with an early increase of p21(CIP1/WAF1) expression and subsequent upregulation of p16(INK4a). The expression of smooth muscle myosin heavy chain-2, which is the molecular marker of highly differentiated SMCs, was reinduced in the Ad,CNP-treated SMCs, The Ad,CNP-treated SMCs also reexpressed particulate guanylate cyclase-A, which shows high affinity to atrial and brain natriuretic peptide and is exclusively expressed in well-differentiated SMCs. CNP, which was overexpressed in rabbit femoral arteries in vivo at the time of balloon injury, significantly suppressed neointimal formation. Furthermore, an enhancement of the expression of smooth muscle myosin heavy chain-2 occurred in the residual neointima. In addition, early regeneration of endothelial cells was observed in the Ad.CNP-infected group. Thus, stimulation of cGMP cascade in proliferating dedifferentiated SMCs can induce growth inhibition and redifferentiation of SMCs with accelerated reendothelialization.