State Key Laboratory of Cardiovascular Disease, Fuwai Hospital & Cardiovascular Institute, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
J Cell Mol Med. 2012 May;16(5):1038-46. doi: 10.1111/j.1582-4934.2011.01414.x.
Up-regulation of insulin-like growth factor 2 receptor (IGF-2R) involved in angiotensin II-induced cell apoptosis in cardiomyoblasts, and correlated with cardiomyocyte apoptosis in hypertensive rat hearts. Here, we detected IGF-2R levels and explored the possible underlying implications in end-stage heart failure (HF) patients before and after heart transplantation. Western blot and immunohistochemistry were used to measure cardiac IGF-2R levels. ELISA was used to detect serum IGF-2R and CD8 levels. Labelling of DNA strand breaks and dihydroethidium detection were used to determine cellular apoptosis and reactive oxygen species, respectively. Cardiac IGF-2R levels increased in end-stage HF patients (n = 11) compared with non-failing control subjects. Leu27-IGF-2, an IGF-2 analogue to activate specially the IGF-2R, could induce apoptosis and reactive oxygen species production in neonatal rat ventricular myocytes. The serum IGF-2R levels were significantly higher in HF patients than those in non-failing control subjects. An unexpected observation is that the serum IGF-2R levels further increased after heart transplantation, peaked at the first month, and gradually reduced close to the levels before heart transplantation at the 6th months after heart transplantation. Serum CD8, a marker of acute rejection, had no change after heart transplantation, but IGF-2R and Granzyme B, as a ligand for the IGF-2R and a marker for CD8 T lymphocyte activation, coexisted in the transplanted hearts. Our preliminary studies suggest that elevation of IGF-2R may participate in pathological process of end-stage HF and involved in the acute cellular rejection after heart transplantation.
胰岛素样生长因子 2 受体（IGF-2R）的上调参与了血管紧张素 II 诱导的心肌细胞凋亡，并且与高血压大鼠心脏中的心肌细胞凋亡相关。在这里，我们检测了 IGF-2R 水平，并在心脏移植前后检测了终末期心力衰竭（HF）患者中的可能潜在意义。使用 Western blot 和免疫组织化学方法测量心脏 IGF-2R 水平。使用 ELISA 检测血清 IGF-2R 和 CD8 水平。使用 DNA 链断裂标记和二氢乙啶检测分别确定细胞凋亡和活性氧。与非衰竭对照组相比，终末期 HF 患者（n=11）的心脏 IGF-2R 水平增加。Leu27-IGF-2 是一种 IGF-2 类似物，可专门激活 IGF-2R，可诱导新生大鼠心室肌细胞凋亡和活性氧产生。HF 患者的血清 IGF-2R 水平明显高于非衰竭对照组。一个意外的观察结果是，心脏移植后血清 IGF-2R 水平进一步升高，在第一个月达到峰值，并在心脏移植后 6 个月逐渐降至心脏移植前的水平。血清 CD8 是急性排斥反应的标志物，心脏移植后没有变化，但 IGF-2R 和 Granzyme B 作为 IGF-2R 的配体和 CD8 T 淋巴细胞活化的标志物共存于移植心脏中。我们的初步研究表明，IGF-2R 的升高可能参与了终末期 HF 的病理过程，并参与了心脏移植后的急性细胞排斥反应。
