Abstract
Heart disease is a leading cause of death with unmet clinical needs for targeted treatment options. Tumor necrosis factor alpha (TNF-α) represents a master pro-inflammatory cytokine that plays an important role in many immunopathogenic processes. Anti-TNF-α therapy is widely used in treating autoimmune inflammatory disorders, but in case of patients with heart disease, this treatment was unsuccessful or even harmful. The underlying reasons remain elusive until today. This review summarizes the effects of anti-TNF-α treatment in patients with and without heart disease and describes the involvement of TNF-α signaling in a number of animal models of cardiovascular diseases. We specifically focused on the role of TNF-α in specific cardiovascular conditions and in defined cardiac cell types. Although some mechanisms, mainly in disease development, are quite well known, a comprehensive understanding of TNF-α signaling in the failing heart is still incomplete. Published data identify pathogenic and cardioprotective mechanisms of TNF-α in the affected heart and highlight the differential role of two TNF-α receptors pointing to the complexity of the TNF-α signaling. In the light of these findings, it seems that targeting the TNF-α pathway in heart disease may show therapeutic benefits, but this approach must be more specific and selectively block pathogenic mechanisms. To this aim, more research is needed to better understand the molecular mechanisms of TNF-α signaling in the failing heart.
Highlights
Heart disease refers to a group of diseases characterized by the affected function of the heart muscle
Diastolic heart failure patients are often characterized by left ventricular ejection fraction (LVEF) > 50%; this type of heart failure is currently defined as heart failure with preserved ejection fraction (HFpEF)
The use of Tumor necrosis factor α (TNF-α) antagonists has been associated with a decreased risk of myocardial infarction [64] and development of acute coronary syndrome [65] pointing to anti-TNF-α treatment as an effective anti-atherosclerotic therapy in rheumatoid arthritis
Summary
Heart disease refers to a group of diseases characterized by the affected function of the heart muscle. Aberrant or impaired cardiac function (heart failure) can develop in the absence of coronary artery disease Such non-ischemic heart disease is a consequence of pathological changes in the structure of the cardiac muscle. For LVEF < 40%, systolic heart function is impaired, and this condition is referred to as heart failure with reduced ejection fraction (HFrEF). Diastolic heart failure patients are often characterized by LVEF > 50% (or sometimes >40%); this type of heart failure is currently defined as heart failure with preserved ejection fraction (HFpEF) Both HFrEF and HFpEF patients show reduced life expectancy [2,3]. The systemic inflammatory condition enhances atherogenesis, leading to coronary artery disease, but it can promote the development of diastolic heart failure.
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