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, IL-6, and IGF-1 by graded
mechanical stress in normal rat myocardium
1 Department of Medicina Clinica, Scienze Cardiovascolari ed Immunologiche, and 2 Department of Scienze Biomorfologiche e Funzionali, Sezione di Anatomia Patologica e Citopatologia, and 3 Department of Biologia e Patologia Cellulare e Molecolare "L. Califano," Facoltà di Medicina e Chirurgia, Università degli Studi di Napoli "Federico II," 80131 Naples; and 4 Department of Medicina Sperimentale e Clinica "G. Salvatore," Facoltà di Medicina e Chirurgia, Università degli Studi di Catanzaro "Magna Grecia," 88100 Catanzaro, Italy
An isovolumic normal
rat heart Langendorff model was used to examine the effects of moderate
(15 mmHg) and severe (35 mmHg) mechanical stretch on the time course
(from 0 to 60 min) of myocardial expression of tumor necrosis factor
(TNF)-
, interleukin (IL)-6, and insulin-like growth factor (IGF)-1
and their cognate receptors. After 10 min of moderate stretch, TNF-
was de novo expressed, whereas constitutive IL-6 and IGF-1 levels were
slightly upregulated; no further changes occurred up to 60 min. In
comparison, severe stretch resulted in a higher and progressive
increase in TNF-, IL-6, and IGF-1 expression up to 20 min. After 20 min, whereas TNF- expression further increased, IL-6 and IGF-1
levels progressively reduced to values lower than those observed under
moderate stretch and in unstretched (5 mmHg) control myocardium (IL-6).
Mechanical stretch did not significantly alter the expression of the
cognate receptors. Indeed, the TNF- receptor (p55) tended to be
progressively upregulated under severe stretch over time. The current
data provide the first demonstration that TNF-, IL-6, and IGF-1
ligand-receptor systems are differentially expressed within the normal
rat myocardium in response to graded mechanical stretch. Such findings
may have potential implications with regard to compensatory hypertrophy and failure.
heart; hemodynamic overload; gene expression
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