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 language | English |
|---|---|
| Pages (from-to) | 696-704 |
| Number of pages | 9 |
| Journal | Hypertension |
| Volume | 56 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Oct 2010 |
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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 journal › Article
}
TY - JOUR
T1 - Intracardiac injection of AdGRK5-NT reduces left ventricular hypertrophy by inhibiting NF-κB-Dependent hypertrophic gene expression
AU - Sorriento, Daniela
AU - Santulli, Gaetano
AU - Fusco, Anna
AU - Anastasio, Antonio
AU - Trimarco, Bruno
AU - Iaccarino, Guido
PY - 2010/10
Y1 - 2010/10
N2 - 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.
AB - 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.
KW - cardiac hypertrophy
KW - intracardiac injection
KW - NF-κB
KW - spontaneously hypertensive rats
KW - transcription factors
UR - http://www.scopus.com/inward/record.url?scp=77957229688&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77957229688&partnerID=8YFLogxK
U2 - 10.1161/HYPERTENSIONAHA.110.155960
DO - 10.1161/HYPERTENSIONAHA.110.155960
M3 - Article
C2 - 20660817
AN - SCOPUS:77957229688
VL - 56
SP - 696
EP - 704
JO - Hypertension
JF - Hypertension
SN - 0194-911X
IS - 4
ER -