McTiernan C F, Feldman A M
Cardiovascular Institute, University of Pittsburgh, Biomedical Science Tower 1744.1, 200 Lothrop Street, Pittsburgh, PA 15213, USA.
Curr Cardiol Rep. 2000 May;2(3):189-97. doi: 10.1007/s11886-000-0068-4.
A variety of clinical and experimental investigations have suggested that tumor necrosis factor alpha (TNF-alpha) may play a role in the pathophysiology of heart failure. Serum levels of TNF-alpha are elevated in patients with heart failure, and both cardiac and infiltrating cells of the myocardium can produce this proinflammatory cytokine. Both cardiac myocytes and nonmyocytes also express receptors for TNF-alpha, and experimental studies on isolated cells, muscles, and transgenic models demonstrate the ability of TNF-alpha to recapitulate functional and biochemical alterations resembling that observed in human congestive heart failure. The intracellular pathways affected by TNF-alpha include production of ceramide and an alteration in calcium metabolism. Recent studies in both animal models and clinical investigations suggest that anti-TNF-alpha therapies may limit the pathophysiologic consequences of congestive heart failure.
多项临床和实验研究表明，肿瘤坏死因子α（TNF-α）可能在心力衰竭的病理生理学中发挥作用。心力衰竭患者血清中TNF-α水平升高，心肌的心肌细胞和浸润细胞均可产生这种促炎细胞因子。心肌细胞和非心肌细胞均表达TNF-α受体，对分离细胞、肌肉和转基因模型的实验研究表明，TNF-α能够重现类似于人类充血性心力衰竭中观察到的功能和生化改变。受TNF-α影响的细胞内途径包括神经酰胺的产生和钙代谢的改变。动物模型和临床研究中的最新研究表明，抗TNF-α疗法可能会限制充血性心力衰竭的病理生理后果。
