Antisense to epidermal growth factor receptor prevents the development of left ventricular hypertrophy.
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.
Kagiyama
Shuntaro
S
Department of Physiology and Functional Genomics, University of Florida, Gainesville 32610-0274, USA.
Qian
Keping
K
Kagiyama
Tomoko
T
Phillips
M Ian
MI
D000818:Animals; D001794:Blood Pressure; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D015316:Genetic Therapy; D006973:Hypertension / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D020319:Oligodeoxyribonucleotides, Antisense / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR
D020319:Oligodeoxyribonucleotides, Antisense; D066246:ErbB Receptors; D020928:Mitogen-Activated Protein Kinases