Transplantation of myoblast sheets that secrete the novel peptide SVVYGLR improves cardiac function in failing hearts
Transplantation of myoblast sheets that secrete the novel peptide SVVYGLR improves cardiac function in failing hearts
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DOI：
10.1093/cvr/cvt088
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发表时间：
2013-07-01
影响因子：
10.8
通讯作者：
Matsuura, Nariaki
中科院分区：
文献类型：
--
作者：
Uchinaka, Ayako;Kawaguchi, Naomasa;Matsuura, Nariaki
成肌细胞片移植是心力衰竭后增强心功能的一种很有前途的治疗方法。我们以前已经证明了骨桥蛋白(SV肽)的7个氨基酸序列(Ser-Val-Val-Tyr-Gly-Leu-Arg)可以诱导血管生成。结扎冠状动脉左前降支2周后，动物分为三组：一组移植野生型大鼠骨骼肌成肌片(WT-rSkms)；一组移植分泌SV的肌成肌细胞片(SV-rSkms)；以及对照组(仅结扎)。我们通过转化生长因子信号传递来评估心功能、组织学变化和平滑肌肌动蛋白(SMA)的表达。SV-rSkM组的射血分数和短轴缩短率明显改善，收缩末期容量的增大也明显减弱。SV-rSkM组的左心室重构(包括纤维化和肥厚)明显减轻，由成肌细胞膜分泌的SV促进了梗塞边缘区域的血管生成。此外，SV-rSkM组在梗死区可见大量SMA阳性细胞群。体外培养的心肌成纤维细胞加入SV后，SMA的表达增加。此外，SV与转化生长因子受体结合，且SV处理激活了转化生长因子受体Smad信号，分泌转化生长因子的成肌细胞膜有助于长期改善心功能。SV可通过转化生长因子-Smad信号通路诱导成纤维细胞向肌成纤维细胞分化。该多肽可作为心脏移植的桥梁或心脏再生治疗的理想多肽药物。
Transplantation of myoblast sheets is a promising therapy for enhancing cardiac function after heart failure. We have previously demonstrated that a 7-amino-acid sequence (Ser-Val-Val-Tyr-Gly-Leu-Arg) derived from osteopontin (SV peptide) induces angiogenesis. In this study, we evaluated the long-term therapeutic effects of myoblast sheets secreting SV in a rat infarction model.Two weeks after ligation of the left anterior descending coronary artery, the animals were divided into the following three groups: a group transplanted with wild-type rat skeletal myoblast sheets (WT-rSkMs); a group transplanted with SV-secreting myoblast sheets (SV-rSkMs); and a control group (ligation only). We evaluated cardiac function, histological changes, and smooth muscle actin (SMA) expression through transforming growth factor- (TGF-) signalling. The ejection fraction and fractional shortening were significantly better, and the enlargement of end-systolic volume was also significantly attenuated in the SV-rSkM group. Left ventricular remodelling, including fibrosis and hypertrophy, was significantly attenuated in the SV-rSkM group, and SV secreted by the myoblast sheets promoted angiogenesis in the infarcted border area. Furthermore, many clusters of SMA-positive cells were observed in the infarcted areas in the SV-rSkM group. In vitro SMA expression was increased when SV was added to the isolated myocardial fibroblasts. Moreover, SV bound to the TGF- receptor, and SV treatment activated TGF- receptorSmad signalling.The SV-secreting myoblast sheets facilitate a long-term improvement in cardiac function. The SV can induce differentiation of fibroblasts to myofibroblasts via TGF-Smad signalling. This peptide could possibly be used as a bridge to heart transplantation or as an ideal peptide drug for cardiac regeneration therapy.