title: Tumor necrosis factor-alpha at acute myocardial infarction in rats and effects on cardiac fibroblasts.
abstract: Tumor necrosis factor-alpha (TNF-alpha) biosynthesis by the myocardium in response to several diseases has not been solely associated with activation of the immune system but may also serve as a stress response in the context of neurohumoral gene activation. In this regard, beneficial as well as adverse effects of the cytokine on injured myocardium have been reported. TNF-alpha has been suggested to modulate myocyte and fibroblast cell growth and function. Now, in a rat model of acute myocardial infarction TNF-alpha expression and effects on cardiac fibroblast were determined. TNF-alpha was detected in rat hearts with acute myocardial infarction, parallel to the presence of proliferating fibroblasts, at the border zone of the infarct region, to a lesser degree in the infarct zone and was still present in the surviving myocardium. Similarly, the TNF-alpha mRNA level was, compared to sham-operated heart, higher in the infarct area. In the remote myocardium, a trend to an elevated TNF-alpha mRNA level was observed. TNF-alpha stimulated proliferation and expression of fibronectin in fibroblasts isolated from the infarct, non-infarct-region and sham-operated hearts. Angiotensin II is mitogenic for fibroblasts post-myocardial infarction and effects might be mediated indirectly by TNF-alpha. Addition of a neutralising anti-TNF-alpha antibody inhibited angiotensin II stimulated proliferation of fibroblasts only from the infarcted myocardium. The regional differences in TNF-alpha protein and mRNA levels, parallel to proliferating fibroblasts and proliferative effects may foster the reparative, reactive and adverse post-infarct remodeling of the heart.
authors.affiliation: II. Medical Clinic, Faculty of Medicine Mannheim, University of Heidelberg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Jacobs
authors.forename: S
authors.initials: S
authors.lastname: Staufenberger
authors.forename: U
authors.initials: U
authors.lastname: Gergs
authors.forename: K
authors.initials: K
authors.lastname: Meuter
authors.forename: K
authors.initials: K
authors.lastname: Brandstätter
authors.forename: M
authors.initials: M
authors.lastname: Hafner
authors.forename: G
authors.initials: G
authors.lastname: Ertl
authors.forename: W
authors.initials: W
authors.lastname: Schorb
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011921:Rats, Inbred WKY; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D014409:Tumor Necrosis Factor-alpha