Cardiac amyloidosis induces up-regulation of Deleted in Malignant Brain Tumors 1 (DMBT1)

Cardiovasc Pathol. 2013 May-Jun;22(3):195-202. doi: 10.1016/j.carpath.2012.10.006. Epub 2012 Dec 4.

Abstract

Background: Amyloidosis is a life-threatening protein misfolding disease and affects cardiac tissue, leading to heart failure, myocardial ischemia and arrhythmia. Amyloid deposits result in oxidative stress, inflammation and apoptosis. The purpose of this study was to examine the role of innate defense components, i.e., Deleted in Malignant Brain Tumors 1 (DMBT1) and the complement system, in different types of cardiac amyloidosis.

Methods: Expression of DMBT1 and of the complement proteins C1q, C3d and C4d in cardiac specimens of patients with different types of amyloidosis were determined by immunohistochemistry and correlated with amyloid deposits stained by Congo red dye.

Results: Strong DMBT1 staining adjacent to amyloid deposits was detected in different amyloidosis types, depending on the extent of the deposits. DMBT1 is localized in the endomysium and perimysium, in the endocardium, in the myocytes and in endothelial cells of affected transmural vessels. C1q, C3d and C4d were detected in the amyloid deposits but also in the endomysium and perimysium, in some myocytes, in endothelial cells, in the endocardium, and around the amyloid deposits.

Conclusions: Up-regulated DMBT1 and complement activation in cardiac amyloidosis may be part of the activated pathways induced by protein aggregation and the consecutive inflammatory reaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amyloidosis / metabolism*
  • Amyloidosis / pathology
  • Calcium-Binding Proteins
  • Complement Activation
  • DNA-Binding Proteins
  • Female
  • Heart Diseases / metabolism*
  • Heart Diseases / pathology
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Receptors, Cell Surface / biosynthesis*
  • Tumor Suppressor Proteins
  • Up-Regulation

Substances

  • Calcium-Binding Proteins
  • DMBT1 protein, human
  • DNA-Binding Proteins
  • Receptors, Cell Surface
  • Tumor Suppressor Proteins