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Antisense to epidermal growth factor receptor prevents the development of left ventricular hypertrophy.

Authors: Kagiyama, S  Qian, K  Kagiyama, T  Phillips, MI 
Citation: Kagiyama S, etal., Hypertension. 2003 Mar;41(3 Pt 2):824-9. Epub 2002 Dec 2.
Pubmed: (View Article at PubMed) PMID:12624003
DOI: Full-text: DOI:10.1161/01.HYP.0000047104.42047.9B

We previously demonstrated that left ventricular hypertrophy (LVH) induced by angiotensin II infusion requires epidermal growth factor receptor (EGFR) activation to mediate the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway. To test whether the EGFR-mediated MAPK/ERK activation plays an important role in development and maintenance of LVH in spontaneously hypertensive rats (SHR), we investigated the effects of antisense oligodeoxynucleotide to EGFR (EGFR-AS) on LVH and blood pressure in young and adult SHR. EGFR-AS, sense oligonucleotide to EGFR (EGFR-S; 1.5 mg/kg), or vehicle control (5% dextrose) with liposome was injected once a week for 2 months in 5- or 13-week-old SHR. The effect of EGFR-AS on the expression of EGFR and phosphorylated ERK in the heart were examined by Western blots. After treatment, EGFR-AS significantly (P<0.05) decreased left ventricular weight/body weight and blood pressure in young SHR compared with EGFR-S or control-treated rats. In adult SHR, EGFR-AS did not affect left ventricular weight/body weight and blood pressure. EGFR and phosphorylated ERK significantly declined from 5 to 20 weeks (P<0.05). EGFR-AS, but not EGFR-S, significantly (P<0.05) decreased the expression of EGFR and phosphorylated ERK in young SHR, but had no significant effect in adult SHR. These results suggests that EGFR-mediated ERK activation is critically important for LVH in young SHR. This may be related to the high levels of EGFR and phosphorylated ERK in young SHR, suggesting a critical role of the EGFR-activated ERK pathway in cardiovascular development but not in the maintenance of established LVH in adult SHR.


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CRRD Object Information
CRRD ID: 1580955
Created: 2006-09-06
Species: All species
Last Modified: 2006-09-06
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.