TNFα in myocardial ischemia/reperfusion, remodeling and heart failure

Abstract

TNFα is crucially involved in the pathogenesis and progression of myocardial ischemia/reperfusion injury and heart failure. The formation and release of TNFα and its downstream signal transduction cascade following activation of its two receptor subtypes are characterized. Myocardial TNFα and TNF receptor activation have an ambivalent role in myocardial ischemia/reperfusion injury and protection from it. Excessive TNFα expression and subsequent cardiomyocyte TNF receptor type 1 stimulation induce contractile dysfunction, hypertrophy, fibrosis and cell death, while a lower TNFα concentration and subsequent cardiomyocyte TNF receptor type 2 stimulation are protective. Apart from its concentration and receptor subtype, the myocardial action of TNFα depends on the duration of its exposure and its localization. While detrimental during sustained ischemia, TNFα contributes to ischemic preconditioning protection, no matter whether it is the first, second or third window of protection, and both TNF receptors are involved in the protective signal transduction cascade. Finally, the available clinical attempts to antagonize TNFα in cardiovascular disease, notably heart failure, are critically discussed.

TNF Receptor 1/2 Predict Heart Failure Risk in Type 2 Diabetes Mellitus Patients

“…In contrast, TNFR2 has an anti-inflammatory and tissue repair effect by countering the effect of TNFR1 on NF-kB and JNK. 18,24) Although NF-kB and JNK are chronically activated in heart failure and diabetes mellitus, there is still disagreement as to whether they have a protective or detrimental role. [25][26][27] However, TNFR1/2 are important bridges for extracellular and intracellular inflammatory responses.…”

“…TNFR1 is the receptor that mediates cell injury apoptosis and death through nuclear factor kB, however, TNFR2 may cause cell migration, proliferation, and restoration to fight the harmful effects of TNFR1. 17,18) An independent association between TNFR1/2 and the risk of HF in diabetes patients has not yet been rigorously established. The aim of this study was to assess the association between sTNFR1 and sTNFR2 levels and incidental HF risk in diabetes patients.…”

The effect of leptin and resveratrol on JAK/STAT pathways and Sirt-1 gene expression in the renal tissue of ischemia/reperfusion induced rats

“…These roles are well presented in liver and myocardiac tissues (8,9). It is also well known that TNF-α plays a critical role in many types of kidney damage and TNF-α Receptor 1 (TNF-α R1) is the key mediator of this role by causing apoptosis (10).…”

Personalized Medicine in Cardiology: State, Problems and Prospects

“…На самом деле, миокардиальный TNF-α и его рецепторы (тип 1 и тип 2) сложным образом участвуют в патогенезе СН. В частно-сти, чрезмерная экспрессия стимуляции рецептора TNF-α 1-го типа может приводить к гипертрофии сердца, фибро-зу, сократительной дисфункции и апоптозу, тогда как более низкая активация TNF-α и рецептора 2-го типа является кардиопротекторной [36]. Исследование 1200 пациентов с СН показало, что уровни TNF-α были непо-средственно связаны со стадией NYHA, а более высокие уровни были связаны с более низким прогнозом [37].…”