Nuclear factor-κB signaling contributes to severe, but not moderate, angiotensin II-induced left ventricular remodeling

Balázs Sármán, Réka Skoumal, Hanna Leskinen, Jaana Rysä, Mika Ilves, Ylermi Soini, Juha Tuukkanen, Sampsa Pikkarainen, Zoltán Lakó-Futó, Beatrix Sármán, Lajos Papp, Rudolf DeChâtel, Miklós Tóth, Heikki Ruskoaho, István Szokodi

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

OBJECTIVE: The transcription factor nuclear factor-kappaB (NF-κB) has been implicated in cardiomyocyte hypertrophy in vitro as well as in vivo; however, it is unknown if activation of NF-κB plays a mandatory role in the hypertrophic process. Here we characterize the importance of NF-κB signaling in moderate and severe left ventricular (LV) hypertrophy in rats with chronic pressure overload induced by angiotensin II (Ang II) infusion. METHODS AND RESULTS: Electrophoretic mobility shift assay analysis revealed that Ang II infusion (2.5 μg/kg per min) for 6 days increased LV NF-κB/DNA-binding activity in a biphasic manner in Sprague-Dawley rats. Pyrrolidine dithiocarbamate (PDTC) (100 mg/kg per day), an NF-κB inhibitor, abolished Ang II-induced NF-κB activation and concomitant increase in tumor necrosis factor-α gene expression, while activator protein-1/DNA binding was not affected. Inhibition of NF-κB signaling for 6 days significantly attenuated Ang II-induced increases in LV/body weight ratio, LV mean wall thickness and cardiomyocyte cross-sectional area, without compromising LV systolic function. Moreover, PDTC abolished Ang II-induced cardiomyocyte apoptosis and interstitial fibrosis, and attenuated the gene expression of type I collagen. In contrast, a moderate LV hypertrophy induced by Ang II at a lower dose (0.5 μg/kg per min) was not associated with a significant activation of NF-κB, and PDTC treatment had no effect on the hypertrophic indices. CONCLUSION: Our in-vivo data indicate a critical role of NF-κB signaling in the advanced stage of the remodeling process, whereas development of moderate LV hypertrophy is not dependent on NF-κB activation.

Original languageEnglish
Pages (from-to)1927-1939
Number of pages13
JournalJournal of hypertension
Volume25
Issue number9
DOIs
Publication statusPublished - Sep 2007

Keywords

  • Angiotensin II
  • Apoptosis
  • Fibrosis
  • Hypertrophy
  • Nuclear factor-κB

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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    Sármán, B., Skoumal, R., Leskinen, H., Rysä, J., Ilves, M., Soini, Y., Tuukkanen, J., Pikkarainen, S., Lakó-Futó, Z., Sármán, B., Papp, L., DeChâtel, R., Tóth, M., Ruskoaho, H., & Szokodi, I. (2007). Nuclear factor-κB signaling contributes to severe, but not moderate, angiotensin II-induced left ventricular remodeling. Journal of hypertension, 25(9), 1927-1939. https://doi.org/10.1097/HJH.0b013e3281e66653