Ca(2+)-binding proteins in dogs with heart failure: effects of cardiac contractility modulation electrical signals

Clin Transl Sci. 2009 Jun;2(3):211-5. doi: 10.1111/j.1752-8062.2009.00097.x.

Abstract

Background: In dogs with heart failure (HF), chronic therapy with cardiac contractility modulation (CCM) electrical signals delivered to left ventricular (LV) muscle during the absolute refractory period improves LV function. This study examined the effects of CCM therapy on the expression of calcium (Ca(2+))-binding proteins (CBPs) in dogs with HF.

Methods and results: Studies were performed in LV tissue from seven CCM-treated HF dogs, seven untreated HF dogs, and six normal (NL) dogs. mRNA expression of S100A1, sorcin, presenillin-1 (PS1), PS2, histidine-rich Ca(2+)-binding protein (HRC), and 18S ribosomal RNA (18S), a housekeeping gene, was measured using RT-PCR. Protein levels of CBPs and calsequestrin (CSQ) were determined by Western blotting. No difference was observed in the expression of 18S and CSQ among study groups. Compared with NL, the expression of S100A1, sorcin, and HRC was decreased, whereas the expression of PS2 was increased in untreated HF dogs. CCM therapy normalized the expression of S100A1, sorcin, and PS2 but not of HRC. No change was seen in the expression of PS1 among study groups.

Conclusion: CCM therapy restores LV expression of S100A1, PS2, and sorcin. Normalization of CBPs may partly contribute to improved LV function in HF following CCM therapy.

MeSH terms

  • Animals
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism*
  • Calsequestrin / genetics
  • Calsequestrin / metabolism
  • Dogs
  • Gene Expression Regulation
  • Heart Conduction System / metabolism*
  • Heart Conduction System / physiopathology*
  • Heart Failure / metabolism*
  • Heart Failure / physiopathology*
  • Heart Ventricles / metabolism
  • Heart Ventricles / physiopathology
  • Myocardial Contraction / physiology*
  • Presenilin-1 / genetics
  • Presenilin-1 / metabolism
  • Presenilin-2 / genetics
  • Presenilin-2 / metabolism
  • RNA, Ribosomal, 18S / genetics
  • RNA, Ribosomal, 18S / metabolism
  • S100 Proteins / genetics
  • S100 Proteins / metabolism

Substances

  • Calcium-Binding Proteins
  • Calsequestrin
  • Presenilin-1
  • Presenilin-2
  • RNA, Ribosomal, 18S
  • S100 Proteins
  • S100A1 protein