Hypophosphorylation of the stiff N2B titin isoform raises cardiomyocyte resting tension in failing human myocardium

A. Borbély, Ines Falcao-Pires, Loek Van Heerebeek, Nazha Hamdani, I. Édes, Cristina Gavina, Adelino F. Leite-Moreira, Jean G F Bronzwaer, Z. Papp, Jolanda Van Der Velden, Ger J M Stienen, Walter J. Paulus

Research output: Contribution to journalArticle

196 Citations (Scopus)

Abstract

High diastolic stiffness of failing myocardium results from interstitial fibrosis and elevated resting tension (Fpassive) of cardiomyocytes. A shift in titin isoform expression from N2BA to N2B isoform, lower overall phosphorylation of titin, and a shift in titin phosphorylation from N2B to N2BA isoform can raise Fpassive of cardiomyocytes. In left ventricular biopsies of heart failure (HF) patients, aortic stenosis (AS) patients, and controls (CON), we therefore related Fpassive of isolated cardiomyocytes to expression of titin isoforms and to phosphorylation of titin and titin isoforms. Biopsies were procured by transvascular technique (44 HF, 3 CON), perioperatively (25 AS, 4 CON), or from explanted hearts (4 HF, 8 CON). None had coronary artery disease. Isolated, permeabilized cardiomyocytes were stretched to 2.2-μm sarcomere length to measure Fpassive. Expression and phosphorylation of titin isoforms were analyzed using gel electrophoresis with ProQ Diamond and SYPRO Ruby stains and reported as ratio of titin (N2BA/N2B) or of phosphorylated titin (P-N2BA/P-N2B) isoforms. F passive was higher in HF (6.1±0.4 kN/m2) than in CON (2.3±0.3 kN/m2; P2; Ppassive of human HF cardiomyocytes.

Original languageEnglish
Pages (from-to)780-786
Number of pages7
JournalCirculation Research
Volume104
Issue number6
DOIs
Publication statusPublished - Mar 27 2009

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Connectin
Cardiac Myocytes
Myocardium
Protein Isoforms
Heart Failure
Phosphorylation
Aortic Valve Stenosis
Biopsy
Sarcomeres
Diamond
Electrophoresis
Coronary Artery Disease
Fibrosis
Coloring Agents
Gels

Keywords

  • Diastole
  • Heart failure
  • Myocardium
  • Titin

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Hypophosphorylation of the stiff N2B titin isoform raises cardiomyocyte resting tension in failing human myocardium. / Borbély, A.; Falcao-Pires, Ines; Van Heerebeek, Loek; Hamdani, Nazha; Édes, I.; Gavina, Cristina; Leite-Moreira, Adelino F.; Bronzwaer, Jean G F; Papp, Z.; Van Der Velden, Jolanda; Stienen, Ger J M; Paulus, Walter J.

In: Circulation Research, Vol. 104, No. 6, 27.03.2009, p. 780-786.

Research output: Contribution to journalArticle

Borbély, A, Falcao-Pires, I, Van Heerebeek, L, Hamdani, N, Édes, I, Gavina, C, Leite-Moreira, AF, Bronzwaer, JGF, Papp, Z, Van Der Velden, J, Stienen, GJM & Paulus, WJ 2009, 'Hypophosphorylation of the stiff N2B titin isoform raises cardiomyocyte resting tension in failing human myocardium', Circulation Research, vol. 104, no. 6, pp. 780-786. https://doi.org/10.1161/CIRCRESAHA.108.193326
Borbély, A. ; Falcao-Pires, Ines ; Van Heerebeek, Loek ; Hamdani, Nazha ; Édes, I. ; Gavina, Cristina ; Leite-Moreira, Adelino F. ; Bronzwaer, Jean G F ; Papp, Z. ; Van Der Velden, Jolanda ; Stienen, Ger J M ; Paulus, Walter J. / Hypophosphorylation of the stiff N2B titin isoform raises cardiomyocyte resting tension in failing human myocardium. In: Circulation Research. 2009 ; Vol. 104, No. 6. pp. 780-786.
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