Intracardiac injection of AdGRK5-NT reduces left ventricular hypertrophy by inhibiting NF-κB-Dependent hypertrophic gene expression

Daniela Sorriento, Gaetano Santulli, Anna Fusco, Antonio Anastasio, Bruno Trimarco, Guido Iaccarino

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

Several studies underline the role of the transcription factor NF-κB in the development of left cardiac hypertrophy (LVH). We have demonstrated recently that the RGS homology domain within the amino terminus of GRK5 (GRK5-NT) is able to inhibit NF-κB transcription activity and its associated phenotypes. The aim of this study was to evaluate the ability of GRK5-NT to regulate LVH through the inhibition of NF-κB both in vitro and in vivo. In cardiomyoblasts, GRK5-NT inhibits phenylephrine-induced transcription of both NF-κB and atrial natriuretic factor promoters, assessed by luciferase assay, thus confirming a role for this protein in the regulation of cardiomyocyte hypertrophy. In vivo, we explored 2 rat models of LVH, the spontaneously hypertensive rat and the normotensive Wistar Kyoto rat exposed to chronic administration of phenylephrine. Intracardiac injection of an adenovirus encoding for GRK5-NT reduces cardiac mass in spontaneously hypertensive rats and prevents the development of phenylephrine-induced LVH in Wistar Kyoto rats. This associates with inhibition of NF-κB signaling (assessed by NF-κB levels), transcriptional activity and phenotypes (fibrosis and apoptosis). Such phenomenon is independent from hemodynamic changes, because adenovirus encoding for GRK5-NT did not reduce blood pressure levels in spontaneously hypertensive rats or in Wistar Kyoto rats. In conclusion, our study supports the regulation of LVH based on the GRK5-NT inhibition of the NF-κB transduction signaling.

Original languageEnglish (US)
Pages (from-to)696-704
Number of pages9
JournalHypertension
Volume56
Issue number4
DOIs
StatePublished - Oct 1 2010

Keywords

  • NF-κB
  • cardiac hypertrophy
  • intracardiac injection
  • spontaneously hypertensive rats
  • transcription factors

ASJC Scopus subject areas

  • Internal Medicine

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