Anti-inflammatory peptides from cardiac progenitors ameliorate dysfunction after myocardial infarction.
Anti-inflammatory peptides from cardiac progenitors ameliorate dysfunction after myocardial infarction.
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DOI：
10.1161/jaha.114.001101
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发表时间：
2014-12-02
影响因子：
5.4
通讯作者：
Kobayashi Y
中科院分区：
文献类型：
--
作者：
Liu ML;Nagai T;Tokunaga M;Iwanaga K;Matsuura K;Takahashi T;Kanda M;Kondo N;Naito AT;Komuro I;Kobayashi Y
心肌细胞治疗已被提出作为治疗心肌梗死的新策略之一。虽然有一些报道显示细胞治疗可以改善缺血心脏的功能，但这些研究的效果各不相同，其有益作用的机制仍然未知。以前，我们报道了克隆干细胞抗原-1阳性心脏祖细胞在移植到缺血心脏时发挥了治疗作用。我们的目的是确定心脏祖细胞特异性旁分泌因子，并阐明其有益作用的机制。通过使用抗体阵列，我们发现可溶性连接粘附分子-A（JAM-A）从心脏祖细胞中大量分泌。用来自培养的心脏祖细胞的条件培养基或可溶性JAM-A预处理嗜中性粒细胞抑制跨内皮迁移并降低嗜中性粒细胞的运动性。这些抑制作用被抗JAM-A中和抗体减弱。心肌前体细胞注射入梗死心脏可减少中性粒细胞浸润和炎性细胞因子的表达。将表达可溶性JAM-A但不表达JAM-A siRNA的心脏祖细胞注射到梗死心脏中可预防心脏重塑并减少纤维化面积。从心脏祖细胞分泌的可溶性JAM-A减少心肌梗死后中性粒细胞的浸润，并通过预防过度炎症来改善组织损伤。我们的发现可能会通过使用JAM-A的抗炎作用为心血管疾病带来新的治疗方法。
Cardiac cell therapy has been proposed as one of the new strategies against myocardial infarction. Although several reports showed improvement of the function of ischemic heart, the effects of cell therapy vary among the studies and the mechanisms of the beneficial effects are still unknown. Previously, we reported that clonal stem cell antigen‐1–positive cardiac progenitor cells exerted a therapeutic effect when transplanted into the ischemic heart. Our aims were to identify the cardiac progenitor‐specific paracrine factor and to elucidate the mechanism of its beneficial effect. By using an antibody array, we found that soluble junctional adhesion molecule‐A (JAM‐A) was abundantly secreted from cardiac progenitor cells. Pretreatment of neutrophils with conditioned medium from cultured cardiac progenitor cells or soluble JAM‐A inhibited transendothelial migration and reduced motility of neutrophils. These inhibitory effects were attenuated by anti–JAM‐A neutralizing antibody. Injection of cardiac progenitor cells into infarct heart attenuated neutrophil infiltration and expression of inflammatory cytokines. Injection of soluble JAM‐A–expressing, but not of JAM‐A siRNA–expressing, cardiac progenitor cells into the infarct heart prevented cardiac remodeling and reduced fibrosis area. Soluble JAM‐A secreted from cardiac progenitor cells reduces infiltration of neutrophils after myocardial infarction and ameliorates tissue damage through prevention of excess inflammation. Our finding may lead to a new therapy for cardiovascular disease by using the anti‐inflammatory effect of JAM‐A.