Merx Marc W, Zernecke Alma, Liehn Elisa A, Schuh Alexander, Skobel Erik, Butzbach Britta, Hanrath Peter, Weber Christian
Medizinische Klinik I, Universitätsklinikum Aachen, Pauwelsstr. 30, 52057 Aachen, Germany.
Basic Res Cardiol. 2005 May;100(3):208-16. doi: 10.1007/s00395-005-0516-9. Epub 2005 Feb 3.
Although cell-based therapy after myocardial infarction (MI) may be beneficial in improving cardiac dysfunction, the underlying mechanisms remain to be clarified. Since human umbilical vein endothelial cells (HUVEC) harbor the potential for transdifferentiation, we studied the functional effects of HUVEC transplantation in a rat model of MI.
HUVEC labeled with BrdU or medium alone were injected into the infarcted area and its margin 4 weeks after ligation of the left coronary artery in cyclosporine-treated rats. BrdU(+) signals could be detected in the area of MI at two weeks and two months after injection only in hearts transplanted with HUVEC. While no signs of transdifferentiation into cardiomyocytes were evident, staining for the rat macrophage marker ED-1, adjacent to or colocalized with BrdU(+) signals, revealed an in.ltration with macrophages and implied the phagocytosis of injected HUVEC. In the vicinity of BrdU(+) signals, the density of CD31(+) microvessels was significantly increased in HUVEC-transplanted as compared to medium-treated hearts after two months. HUVEC transplantation led to improved contractility as assessed by echocardiography and to higher coronary flow rates as well as to improved response to volume strain and catecholamine stress in Langendorff perfused hearts.
After MI, transplanted HUVEC persist in the host myocardium and trigger an infiltration with macrophages. The ensuing increase in neovascularization and improvement in global left ventricular function may be attributable to the associated inflammatory response.
尽管心肌梗死（MI）后基于细胞的治疗可能有助于改善心脏功能障碍，但其潜在机制仍有待阐明。由于人脐静脉内皮细胞（HUVEC）具有转分化的潜力，我们研究了HUVEC移植在大鼠MI模型中的功能效应。
在环孢素处理的大鼠中，于左冠状动脉结扎4周后，将用BrdU标记的HUVEC或单独的培养基注射到梗死区域及其边缘。仅在移植了HUVEC的心脏中，注射后两周和两个月时在MI区域可检测到BrdU（+）信号。虽然没有明显的向心肌细胞转分化的迹象，但与BrdU（+）信号相邻或共定位的大鼠巨噬细胞标志物ED-1染色显示有巨噬细胞浸润，并提示注射的HUVEC被吞噬。两个月后，与培养基处理的心脏相比，在HUVEC移植的心脏中，BrdU（+）信号附近CD31（+）微血管的密度显著增加。通过超声心动图评估，HUVEC移植导致收缩功能改善，冠状动脉血流速度提高，并且在Langendorff灌注心脏中对容量负荷和儿茶酚胺应激的反应也得到改善。
MI后，移植的HUVEC在宿主心肌中持续存在并引发巨噬细胞浸润。随后新血管形成增加和整体左心室功能改善可能归因于相关的炎症反应。
