Department of Cardiac Surgery and Transplantation at the Medical University of Silesia, Silesian Centre for Heart Disease, Zabrze, Poland.
Exp Gerontol. 2013 Feb;48(2):223-8. doi: 10.1016/j.exger.2012.09.002. Epub 2012 Sep 12.
Disturbed glucose metabolism, particularly in diabetes type 2 (DM2), may result in advanced glycation end product (AGE) formation. One of the possible targets for this reaction is lipofuscin (LF), an intracytoplasmic garbage presumed to be a marker of physiologic and preterm aging of cells. The study was performed to seek for a relationship between AGE and LF in cardiocytes of the failing hearts.
Archived tissue samples from 136 hearts explanted before transplantation (in 14 pts. with ischemic cardiomyopathy (CM) and DM2; 8 pts. with dilated CM and DM2; 67 non-diabetic pts. with ischemic CM; 47 non-diabetic pts. with dilated CM), 14 autopsy cases with DM2, and 20 heart donors (control group) were involved in the study. Immunohistochemical localization of AGE was applied. The coexistence of lipofuscin and AGE was studied by LF autofluorescence in AGE-positive slides.
LF granules inside AGE deposits were present in all studied groups with varying frequencies, but the differences were non-significant. LF granules joined significantly with dispersed patterns of AGE i.e. diffuse and mixed, whereas coincidence of LF and AGE forming granular pattern was rare.
We demonstrate that LF may belong to the components of the AGE deposits. The frequency of this phenomenon is dependent on the AGE dispersion grade, but neither on diabetes nor cardiomyopathy presence.
葡萄糖代谢紊乱,尤其是 2 型糖尿病(DM2),可能导致晚期糖基化终产物(AGE)的形成。这种反应的一个可能的靶标是脂褐素(LF),一种细胞内的垃圾,被认为是细胞生理和早产龄的标志物。本研究旨在探讨衰竭心脏中心肌细胞中 AGE 与 LF 之间的关系。
本研究纳入了 136 例移植前心脏标本(14 例缺血性心肌病(CM)和 DM2 患者;8 例扩张型 CM 和 DM2 患者;67 例非糖尿病缺血性 CM 患者;47 例非糖尿病扩张型 CM 患者),14 例 DM2 尸检病例和 20 例心脏供体(对照组)。应用免疫组织化学定位 AGE。通过 AGE 阳性切片中的 LF 自发荧光研究 LF 和 AGE 的共存。
在所有研究组中,均可见到 AGE 沉积内的 LF 颗粒,但频率不同,差异无统计学意义。LF 颗粒与弥散型 AGE(即弥漫型和混合型)显著结合,而 LF 与形成颗粒型 AGE 的巧合则很少见。
我们证明 LF 可能属于 AGE 沉积的组成部分。这种现象的频率取决于 AGE 的弥散程度,但与糖尿病或心肌病的存在无关。