Open AccessElevation of IGF‐2 receptor and the possible underlying implications in end‐stage heart failure patients before and after heart transplantation
Author(s) -
Wei Yingjie,
Li Jun,
Huang Jie,
Zhang Xiaoling,
Zhao Hong,
Cui Chuanjue,
Li Yishi,
Hu Shengshou
Publication year - 2012
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2011.01414.x
Subject(s) - transplantation , medicine , heart transplantation , heart failure , endocrinology , cd8 , receptor , angiotensin ii , apoptosis , biology , immunology , immune system , biochemistry
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.