title: Antisense to epidermal growth factor receptor prevents the development of left ventricular hypertrophy.
abstract: 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.
authors.affiliation: Department of Physiology and Functional Genomics, University of Florida, Gainesville 32610-0274, USA.
authors.forename: Shuntaro
authors.initials: S
authors.lastname: Kagiyama
authors.forename: Keping
authors.initials: K
authors.lastname: Qian
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kagiyama
authors.forename: M Ian
authors.initials: MI
authors.lastname: Phillips
mesh_terms: 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
chemical_list: D020319:Oligodeoxyribonucleotides, Antisense; D066246:ErbB Receptors; D020928:Mitogen-Activated Protein Kinases