Severity of left ventricular dysfunction in heart failure patients affects the degree of serum-induced cardiomyocyte apoptosis. Importance of inflammatory response and metabolism

Claudia Consoli, Lucia Gatta, Ferdinando Iellamo, Francesca Molinari, Giuseppe M C Rosano, Lionel N J L Marlier

Research output: Contribution to journalArticle

Abstract

Background/Objectives: In heart failure pro-inflammatory cytokines contribute to cardiomyocytes loss by apoptosis and play a role in the remodelling of the extracellular matrix (ECM). Myocardial injury recruits endothelial progenitor cells (EPCs) to the site of damage and stimulates their differentiation, contributing to myocardial tissue repair. We investigated if the severity of left ventricular dysfunction in heart failure patients (HF) may influence the ability of serum to induce cardiomyocytes death and whether this effect is affected by inflammation and intracellular oxidative stress pathways. Methods: Adult murine cardiomyocytes HL-5 were incubated with 2% human serum from patients with heart failure (NYHA classes I to IV). Apoptosis was analysed by two different methods. TNF-α, IL-1β, IL-6, matrix metalloproteinase 1 (MMP-1) and tissue inhibitor of metalloproteinases 1 (TIMP-1) were measured in sera from patients. Results: Cytokine levels were higher in sera from moderate-severe CHF compared to that of patients with mild CHF. Levels of CD117+ (c-Kit+) cells and EPCs were significantly lower in blood from moderate-severe HF patients. Serum from HF patients induced a significantly higher ROS production involving p38 MAPK signalling and apoptosis in cardiomyocytes. NAC treatment prevented serum-induced oxidative effects. The increase of AMPK phosphorylation showed an involvement of FFA β-oxidation during apoptotic stress. Conclusions: All these alterations could be used as predictive factors of worsening in heart failure and culture of cardiomyocytes could be employed to test pharmacological effects.

Original languageEnglish
Pages (from-to)2859-2866
Number of pages8
JournalInternational Journal of Cardiology
Volume167
Issue number6
DOIs
Publication statusPublished - 2013

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Keywords

  • Apoptosis
  • Cardiomyocytes
  • FFA oxidation
  • Heart failure
  • Inflammation
  • Oxidative stress

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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