Abstract
Inflammation has emerged as an important contributor to heart failure (HF) development and progression. Current research data highlight the diversity of immune cells, proteins, and signaling pathways involved in the pathogenesis and perpetuation of heart failure. Chronic inflammation is a major cardiovascular risk factor. Proinflammatory signaling molecules in HF initiate vicious cycles altering mitochondrial function and perturbing calcium homeostasis, therefore affecting myocardial contractility. Specific anti-inflammatory treatment represents a novel approach to prevent and slow HF progression. This review provides an update on the putative roles of inflammatory mediators involved in heart failure (tumor necrosis factor-alpha; interleukin 1, 6, 17, 18, 33) and currently available biological and non-biological therapy options targeting the aforementioned mediators and signaling pathways. We also highlight new treatment approaches based on the latest clinical and experimental research.
Highlights
Heart failure (HF) is linked to increased mortality, frequent hospitalizations, and poor quality of life, showing a significant increase in age-adjusted prevalence
Several proinflammatory cytokines and chemokines, such as TNF-α, interleukin 1β (IL-1β), interleukin 6 (IL-6), interleukin 18 (IL-18), or monocyte chemoattractant protein 1 (MCP-1), are intensely synthesized and released in heart failure with preserved ejection fraction (HFpEF), and their plasma levels are proportional with the organ deterioration [10]
In the CANTOS (Canakinumab Anti-Inflammatory Thrombosis Outcomes Study) trial, patients with prior myocardial infarction and elevated high-sensitivity C-reactive protein levels, treated with 150 mg canakinumab, a human anti-IL-1β monoclonal antibody, every 3 months during followup, showed a 15% relative risk reduction in the primary composite endpoint of death, nonfatal stroke, and nonfatal myocardial infarction compared to patients receiving standard treatment [68]
Summary
Heart failure (HF) is linked to increased mortality, frequent hospitalizations, and poor quality of life, showing a significant increase in age-adjusted prevalence. Numerous experimental studies and clinical trials targeted various local and systemic inflammatory biomarkers and immune cells for the purposes of reducing systemic inflammation and improving myocardial function but showed inconsistent results. Several proinflammatory cytokines and chemokines, such as TNF-α, interleukin 1β (IL-1β), interleukin 6 (IL-6), interleukin 18 (IL-18), or monocyte chemoattractant protein 1 (MCP-1), are intensely synthesized and released in HFpEF, and their plasma levels are proportional with the organ deterioration [10] These cytokines might originate in cardiac structural cells, such as cardiomyocytes, endothelial cells, or fibroblasts, and from infiltrating inflammatory cells, like macrophages or extracardiac tissues [12]. Structural alterations comprise cardiomyocyte hypertrophy, a myofibroblastic transformation of cardiac fibroblasts, along with reactive extracellular fibrosis This remodeling impairs both systolic and diastolic functions of the heart, increasing the risk of proarrhythmia. The drug did not affect normal hearts and did not modify cardiolipin composition [24]
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