The failing human heart is characterized by decreased numbers of telocytes as result of apoptosis and altered extracellular matrix composition

J Cell Mol Med. 2015 Nov;19(11):2597-606. doi: 10.1111/jcmm.12664. Epub 2015 Aug 26.

Abstract

Telocytes (TCs) are a novel type of interstitial cells only recently described. This study aimed at characterizing and quantifying TCs and telopodes (Tps) in normal and diseased hearts. We have been suggested that TCs are influenced by the extracellular matrix (ECM) composition. We used transmission electron microscopy and c-kit immunolabelling to identify and quantify TCs in explanted human hearts with heart failure (HF) because of dilated, ischemic or inflammatory cardiomyopathy. LV myectomy samples from patients with aortic stenosis with preserved ejection fraction and samples from donor hearts which could not be used for transplantation served as controls. Quantitative immunoconfocal analysis revealed that 1 mm(2) of the normal myocardium contains 14.9 ± 3.4 TCs and 41.6 ± 5.9 Tps. As compared with the control group, the number of TCs and Tps in HF decreased more than twofold. There were no differences between HF and control in the number of Ki67-positive TCs. In contrast, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling-positive TCs increased threefold in diseased hearts as compared to control. Significant inverse correlations were found between the amount of mature fibrillar collagen type I and the number of TCs (r = -0.84; P < 0.01) and Tps (r = -0.85; P < 0.01). The levels of degraded collagens showed a significant positive relationship with the TCs numbers. It is concluded that in HF the number of TCs are decreased because of higher rates of TCs apoptosis. Moreover, our results indicate that a close relationship exists between TCs and the ECM protein composition such that the number of TCs and Tps correlates negatively with the amount of mature fibrillar collagens and correlates positively with degraded collagens.

Keywords: extracellular matrix; heart failure; myocardial remodelling; telocytes; telopodes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Cell Count
  • Extracellular Matrix Proteins / analysis
  • Fibrillar Collagens / analysis*
  • Heart Failure / metabolism
  • Heart Failure / pathology*
  • Humans
  • Immunologic Techniques
  • Microscopy, Electron, Transmission
  • Telocytes / pathology*

Substances

  • Extracellular Matrix Proteins
  • Fibrillar Collagens