title: Elevation of IGF-2 receptor and the possible underlying implications in end-stage heart failure patients before and after heart transplantation.
abstract: 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.
authors: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital & Cardiovascular Institute, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China. weiyingjiefw@126.com
authors: Yingjie
authors: Y
authors: Wei
authors: Jun
authors: J
authors: Li
authors: Jie
authors: J
authors: Huang
authors: Xiaoling
authors: X
authors: Zhang
authors: Hong
authors: H
authors: Zhao
authors: Chuanjue
authors: C
authors: Cui
authors: Yishi
authors: Y
authors: Li
authors: Shengshou
authors: S
authors: Hu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016827:CD8 Antigens / Q000097:blood; D053960:DNA Breaks; D005260:Female; D053804:Granzymes / Q000032:analysis; D006333:Heart Failure / Q000378:metabolism*; D016027:Heart Transplantation; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D051381:Rats; D017382:Reactive Oxygen Species / Q000032:analysis; D017527:Receptor, IGF Type 2 / Q000097:blood / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016827:CD8 Antigens; D007376:Interleukin-2; D017382:Reactive Oxygen Species; D017527:Receptor, IGF Type 2; D053804:Granzymes