Phenylephrine and endothelin-1 upregulate connective tissue growth factor in neonatal rat cardiac myocytes.
Cardiac hypertrophy is associated with hypertrophic growth of cardiac myocytes and increased fibrosis. Much is known of the stimuli which promote myocyte hypertrophy and the changes associated with the response, but the links between the two are largely unknown. Using subtractive hybridization, we identified three genes which are acutely (<1 h) upregulated in neonatal rat ventricular myocytes exposed to the alpha-adrenergic agonist, phenylephrine. One represented connective tissue growth factor (CTGF) which is implicated in fibrosis and promotes hypertrophy in other cells. We further examined the expression of CTGF mRNA and protein in cardiac myocytes using quantitative PCR and immunoblotting, confirming that phenylephrine increased CTGF mRNA (maximal within 1 h) and protein (increased over 4 - 24 h). Endothelin-1 promoted a greater, though transient, increase in CTGF mRNA, but the increase in CTGF protein was sustained over 8 h. Neither agonist increased CTGF mRNA in cardiac non-myocytes. By increasing the expression of CTGF in cardiac myocytes, hypertrophic agonists such as phenylephrine and endothelin-1 may promote fibrosis. CTGF may also propagate the hypertrophic response initiated by these agonists.
NHLI Division, Faculty of Medicine, Imperial College London, Flowers Building, Armstrong Road, London SW7 2AZ, UK.
Timothy J
TJ
Kemp
Ioanna-Katerina
IK
Aggeli
Peter H
PH
Sugden
Angela
A
Clerk
D000818:Animals; D000831:Animals, Newborn; D055513:Connective Tissue Growth Factor; D019332:Endothelin-1 / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006352:Heart Ventricles / Q000378:metabolism; D017874:Immediate-Early Proteins / Q000096:biosynthesis* / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D032383:Myocytes, Cardiac / Q000737:chemistry / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D015854:Up-Regulation
C526316:CCN2 protein, rat; D019332:Endothelin-1; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D055513:Connective Tissue Growth Factor; D010656:Phenylephrine