Laboratory for Cardiovascular Research, Center for Anatomy and Cell Biology, Medical University of Vienna, Vienna, Austria.
J Thorac Cardiovasc Surg. 2011 May;141(5):1238-45. doi: 10.1016/j.jtcvs.2010.10.054. Epub 2011 Feb 16.
Transplant of skeletal myoblasts is an attractive alternative to repair irreversibly damaged myocardium in ischemic heart failure. We investigated whether transplant of myoblasts overexpressing placental growth factor would stimulate angiogenesis and enhance myoblast survival in a rat heart failure model.
Three weeks after myocardial infarction, Sprague-Dawley rats in heart failure received intramyocardial injections of Ringer solution (control) or autologous myoblasts, unmodified or transfected with placental growth factor expression plasmid. Sham-operated animals served as noninfarct controls. Cardiac function was assessed by echocardiography to 86 days after engraftment. Immunocytochemistry and fluorescence imaging were used to investigate vessel formation, grafted myoblast survival, infarct wall thickness, and infarct size. Quantitative real-time reverse transcriptase polymerase chain reaction and Western blotting measured tissue messenger RNA and protein expressions.
Left ventricular function significantly improved with time, and fractional shortening on day 86 was significantly enhanced in transfected myoblast group relative to control (P < .01) and unmodified myoblast (P < .05) groups. Vascular density (P < .01) and myoblast survival (P < .05) were enhanced in rats treated with transfected myoblasts relative to other groups (P < .05). Mean fraction of fibrotic scar tissue was decreased in unmodified and transfected myoblast groups relative to controls on day 86 (P < .05), and left ventricular wall thickness was significantly increased in transfected myoblast group relative to other groups (P < .05).
Intramyocardial injections of autologous myoblasts overexpressing placental growth factor improved cardiac function, attenuated adverse cardiac remodeling, induced angiogenesis, and probably enhanced survival of grafted myoblasts.
骨骼肌母细胞移植是修复缺血性心力衰竭中不可逆损伤的心肌的一种有吸引力的替代方法。我们研究了过表达胎盘生长因子的成肌细胞移植是否会刺激血管生成并增强大鼠心力衰竭模型中成肌细胞的存活。
心肌梗死后 3 周，心力衰竭的 Sprague-Dawley 大鼠接受心肌内注射林格溶液（对照）或未经修饰或转染胎盘生长因子表达质粒的自体成肌细胞。假手术动物作为非梗死对照。移植后 86 天通过超声心动图评估心功能。免疫细胞化学和荧光成像用于研究血管形成、移植成肌细胞存活、梗死壁厚度和梗死面积。实时定量逆转录聚合酶链反应和 Western 印迹用于测量组织信使 RNA 和蛋白表达。
左心室功能随时间显著改善，转染成肌细胞组的 86 天的射血分数明显高于对照组（P <.01）和未经修饰的成肌细胞组（P <.05）。与其他组相比，转染成肌细胞组的血管密度（P <.01）和成肌细胞存活（P <.05）均增强。未经修饰和成肌细胞组的纤维化瘢痕组织比例在第 86 天均低于对照组（P <.05），转染成肌细胞组的左心室壁厚度明显高于其他组（P <.05）。
过表达胎盘生长因子的自体成肌细胞心肌内注射可改善心功能，减轻心脏不良重构，诱导血管生成，并可能增强移植成肌细胞的存活。
