Satoh Mamoru, Minami Yoshitaka, Takahashi Yuji, Nakamura Motoyuki
Department of Internal Medicine II and Memorial Heart Center, Iwate Medical University School of Medicine, Uchimaru 19-1, Morioka 020-8505, Iwate, Japan.
Curr Heart Fail Rep. 2008 Jun;5(2):69-74. doi: 10.1007/s11897-008-0012-2.
Recent studies have determined that expression of inflammatory mediators, such as cytokines and chemokines, is an important factor in the development and progression of heart failure (HF). These inflammatory mediators are expressed in response to various myocardial insults, including myocardial ischemia, viral infection, and toxins, and appear to have a detrimental effect on cardiac function and prognosis in HF patients. Our previous reports have shown activation of inflammatory cytokines, particularly tumor necrosis factor-alpha (TNF-alpha), in the myocardium and peripheral monocytes in patients with HF. Indeed, sustained increases in cytokines, including TNF-alpha and its receptor, lead to monocyte phenotype transition, myocytic apoptosis, and activation of matrix metalloproteinase. This in turn modifies the interstitial matrix, augmenting further ventricular remodeling. Thus, in view of the emerging importance of TNF-alpha in the pathogenesis of HF, we review the effects of TNF-alpha on the physiology of the heart and the development of clinical strategies to target the inflammatory cytokine cascade.
最近的研究已确定，炎症介质如细胞因子和趋化因子的表达是心力衰竭（HF）发生和发展的一个重要因素。这些炎症介质是在各种心肌损伤（包括心肌缺血、病毒感染和毒素）的刺激下表达的，并且似乎对HF患者的心脏功能和预后具有有害影响。我们之前的报告显示，HF患者的心肌和外周单核细胞中炎症细胞因子，特别是肿瘤坏死因子-α（TNF-α）被激活。事实上，包括TNF-α及其受体在内的细胞因子持续增加会导致单核细胞表型转变、心肌细胞凋亡以及基质金属蛋白酶激活。这进而改变间质基质，进一步加剧心室重塑。因此，鉴于TNF-α在HF发病机制中的重要性日益凸显，我们综述了TNF-α对心脏生理学的影响以及针对炎症细胞因子级联反应的临床策略的发展。
