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

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
Pages (from-to)696-704
Number of pages9
JournalHypertension
Volume56
Issue number4
DOIs
Publication statusPublished - Oct 2010

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Inbred WKY Rats
Left Ventricular Hypertrophy
Phenylephrine
Inbred SHR Rats
Gene Expression
Adenoviridae
Injections
Phenotype
Cardiomegaly
Atrial Natriuretic Factor
Luciferases
Cardiac Myocytes
Hypertrophy
Fibrosis
Transcription Factors
Hemodynamics
Apoptosis
Blood Pressure
Proteins

Keywords

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

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Intracardiac injection of AdGRK5-NT reduces left ventricular hypertrophy by inhibiting NF-κB-Dependent hypertrophic gene expression. / Sorriento, Daniela; Santulli, Gaetano; Fusco, Anna; Anastasio, Antonio; Trimarco, Bruno; Iaccarino, Guido.

In: Hypertension, Vol. 56, No. 4, 10.2010, p. 696-704.

Research output: Contribution to journalArticle

Sorriento, Daniela ; Santulli, Gaetano ; Fusco, Anna ; Anastasio, Antonio ; Trimarco, Bruno ; Iaccarino, Guido. / Intracardiac injection of AdGRK5-NT reduces left ventricular hypertrophy by inhibiting NF-κB-Dependent hypertrophic gene expression. In: Hypertension. 2010 ; Vol. 56, No. 4. pp. 696-704.
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