alpha 1-Adrenergic stimulation of FGF-2 promoter in cardiac myocytes and in adult transgenic mouse hearts

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 276; no. 3; pp. H826 - H833
• Main Authors: Detillieux, Karen A, Meij, Johanna T. A, Kardami, Elissavet, Cattini, Peter A
• Format: Journal Article
• Language: English
• Published: 01.03.1999
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.1999.276.3.H826

1  Department of Physiology and 2  Department of Human Anatomy and Cell Sciences, Institute of Cardiovascular Science, St. Boniface Hospital Research Center, University of Manitoba, Winnipeg, Manitoba, Canada R3E 3J7 Fibroblast growth factor (FGF-2), a mitogenic, angiogenic, and cardioprotective agent, is reported to be released from the postnatal heart by a mechanism of transient remodeling of the sarcolemma during contraction. This release can be increased with adrenergic stimulation. RNA blotting was used to assess whether FGF-2 synthesis in neonatal rat cardiomyocytes might also be regulated by adrenergic stimulation. FGF-2 RNA levels were increased after treatment with norepinephrine for 6 h or with the -adrenergic agonist phenylephrine for 48 h. To assess an effect on transcription, neonatal rat cardiomyocytes were transfected with a hybrid rat FGF-2 promoter/luciferase gene ( 1058FGFp. luc ) and treated with norepinephrine or phenylephrine for 6 or 48 h, respectively. FGF-2 promoter activity was increased two- to sevenfold in an 1 -specific manner. Putative phenylephrine-responsive elements (PEREs) were identified at positions 780 and 761 relative to a major transcription initiation site. However, deletion analysis of 1058FGFp. luc showed that the phenylephrine response was independent of the putative PEREs, cell contraction, and Ca 2+ influx. In transgenic mice expressing 1058FGFp. luc , a significant three- to sevenfold stimulation of FGF-2 promoter activity was detected in the hearts of two independent lines 6 h after intraperitoneal administration of phenylephrine (50 mg/kg). This increase was still apparent at 24 h but was not detected at 48 h posttreatment. Analysis of FGF-2 mRNA in normal mouse hearts revealed accumulation of the 6.1-kb transcript at 24 h. Control of local FGF-2 synthesis at the transcriptional level through adrenergic stimulation may be important in the response to injury as well as in the maintenance of a healthy myocardium. basic fibroblast growth factor; rat fibroblast growth factor-2 gene; phenylephrine; gene transfer