Growth hormone induces myocardial expression of creatine transporter and decreases plasma levels of IL-1beta in rats during early postinfarct cardiac remodeling.
Growth hormone has been proposed as a potential new therapeutic agent for treatment of myocardial infarction (MI) and congestive heart failure (CHF). The purpose of this study was to evaluate the effects of GH on: (a) myocardial expression of creatine transporter (CreaT) during early postinfarct remodeling, (b) myocardial levels of total creatine (TCr) and adenine pool (TAN) and (c) plasma levels of inflammatory cytokines interleukin-1beta (IL-1beta), tumor-necrosis-factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in rat model of postinfarct cardiac remodeling. Myocardial infarction (MI) was induced by ligation of the left coronary artery in male Sprague-Dawley rats (200-250 g). Three different groups were studied: MI rats treated with GH (n=11) (3 mg/kg/day), MI rats treated with saline (n=10), and sham operated rats (n=7). In the myocardium from GH treated rats the level of mRNA CreaT expression was significantly increased (p<0.01). There was no difference in TCr between the rats with MI and sham-operated rats. Treatment with GH had no effect on TCr. GH had no effect on TAN in left ventricle. All three groups had similar levels of IL-6 and TNF-alpha in plasma. In the rats with MI, treatment with GH normalized the levels of IL-1beta (p<0.05). In conclusion GH increased the expression of CreaT and decreased levels of plasma IL-1beta during postinfarct remodeling in rats. These mechanisms may be responsible for the previously reported beneficial effects of GH on myocardial energy metabolism and preservation of cardiac function in the settings of postinfarct remodeling and CHF.
Omerovic
Elmir
E
Wallenberg Laboratory, Sahlgrenska Academy at Gothenburg University, Sahlgrenska University Hospital, 413 45 Gothenburg, Sweden.
Bollano
Entela
E
Lorentzon
Malin
M
Walser
Marion
M
Mattsson-Hultén
Lillemor
L
Isgaard
Jörgen
J
D000818:Animals; D013006:Growth Hormone / Q000494:pharmacology*; D007375:Interleukin-1 / Q000097:blood*; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D009203:Myocardial Infarction / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020257:Ventricular Remodeling
D007375:Interleukin-1; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; C080679:creatine transporter; D013006:Growth Hormone