Antisense to Epidermal Growth Factor Receptor Prevents the Development of Left Ventricular Hypertrophy

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 41; no. 3, Part 2 Suppl; pp. 824 - 829
• Main Authors: Kagiyama, Shuntaro, Qian, Keping, Kagiyama, Tomoko, Phillips, M Ian
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.03.2003; Hagerstown, MD Lippincott
• Subjects: Animals; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Blood Pressure; Cardiology. Vascular system; Experimental diseases; Genetic Therapy; Hypertension - complications; Hypertension - metabolism; Hypertension - physiopathology; Hypertrophy, Left Ventricular - etiology; Hypertrophy, Left Ventricular - metabolism; Hypertrophy, Left Ventricular - prevention & control; Medical sciences; Mitogen-Activated Protein Kinases - metabolism; Oligodeoxyribonucleotides, Antisense - therapeutic use; Rats; Rats, Inbred SHR; Receptor, Epidermal Growth Factor - biosynthesis; Receptor, Epidermal Growth Factor - genetics; Receptor, Epidermal Growth Factor - physiology; Heart; Rat; Body weight; hypertrophy, left ventricular; protein kinases; Cardiovascular disease; Prevention; Epidermal growth factor; Heart disease; Human; Hypertension; blood pressure; receptors, epidermal; Enzyme; Transferases; Rodentia; Dextrose; Left ventricle; Vertebrata; Growth factor receptor; Mammalia; Treatment; Protein kinase; Animal; Young adult; Angiotensin; Gene therapy; Hypertrophy; antisense
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.HYP.0000047104.42047.9B

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.