Tumor necrosis factor-alpha at acute myocardial infarction in rats and effects on cardiac fibroblasts.

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.