Reference - Detail
|Author||Fujino T, Hasebe N, Fujita M, Takeuchi K, Kawabe J, Tobise K, Higashiyama S, Taniguchi N, Kikuchi K.|
|Title||Enhanced expression of heparin-binding EGF-like growth factor and its receptor in hypertrophied left ventricle of spontaneously hypertensive rats.|
OBJECTIVES:Although heparin-binding epidermal growth factor-like growth factor (HB-EGF) is thought to produce hypertrophy in isolated cardiomyocytes via an autocrine mechanism, the pathophysiological role of HB-EGF, in myocardial hypertrophy in vivo, is not yet known. To investigate the involvement of HB-EGF in cardiac remodeling associated with hypertension in vivo, we assayed the expression of HB-EGF mRNA and protein in the left ventricle (LV) during the development of left ventricular hypertrophy in spontaneously hypertensive rats (SHR).
METHODS:Prior to sacrifice and assay of HB-EGF and EGF-receptor (EGF-R) mRNA, morphologic and hemodynamic variables were measured in SHR and in age-matched Wistar Kyoto rats (WKY). At 5, 9 and 12 weeks of age, rats were killed, their hearts were removed, and the expression of HB-EGF and EGF-R mRNA and protein were measured. In addition, SHR and WKY were treated with enalapril, atenolol, or both for 4 weeks.
RESULTS:In untreated SHR, double products (i.e. systolic blood pressure (sBP) multiplied by heart rate (HR), an index of mechanical load, peaked at 9 weeks. Expression of HB-EGF mRNA was also observed to peak in these animals at 9 weeks, while expression of EGF-R mRNA increased from 5 to 9 weeks, but remained constant thereafter. In untreated WKY, double products and EGF-R mRNA expression did not change over time, whereas the level of HB-EGF message increased gradually. Antibody to HB-EGF reacted primarily with myocyte membranes in SHR, whereas antibody to EGF-R reacted mainly with interstitial cells in these animals. The angiotensin-converting enzyme inhibitor, enalapril, markedly decreased sBP in SHR, whereas the beta 1-adrenoreceptor antagonist, atenolol, significantly decreased HR. While neither alone affected the expression of HB-EGF mRNA, their combination significantly reduced the expression of HB-EGF mRNA, as well as double products, in these rats, but had no effect on expression of EGF-R mRNA.
CONCLUSIONS:The enhanced expression of HB-EGF mRNA and protein in LV of SHR suggest that this growth factor may play an important role during the early development of LV hypertrophy and cardiac fibrosis in SHR. The association between double products and HB-EGF expression suggest that the latter may be induced by increased mechanical load and may contribute, in turn, to cardiac remodeling.
|MeSH||Adrenergic beta-Antagonists / pharmacology Angiotensin-Converting Enzyme Inhibitors / pharmacology Animals Antibodies / metabolism Atenolol / pharmacology Biomechanical Phenomena Drug Synergism Enalapril / pharmacology Epidermal Growth Factor / analysis Epidermal Growth Factor / genetics Epidermal Growth Factor / metabolism* ErbB Receptors / analysis ErbB Receptors / genetics ErbB Receptors / metabolism* Heparin-binding EGF-like Growth Factor Hypertrophy, Left Ventricular / metabolism* Intercellular Signaling Peptides and Proteins Male Myocardium / chemistry Myocardium / metabolism* RNA, Messenger / analysis Rats Rats, Inbred SHR Rats, Inbred WKY|
|WOS Category||CARDIAC & CARDIOVASCULAR SYSTEMS|
|DNA material||pco12 EGFR Human EGF receptor cDNA (RDB01276)|