Immune mechanisms in heart failure

Abstract

Elevated levels of circulating pro-inflammatory biomarkers in patients with both ischaemic and non-ischaemic heart failure (HF) correlate with disease severity and prognosis. Experimental studies have shown activation of immune response mechanisms in the heart to provoke cardiac adverse remodelling and cause left ventricular dysfunction. Consequently, most of the clinical trials targeting elements of the immune response in HF attempted to modulate the inflammatory response. Surprisingly, clinical studies targeting immune effectors were either neutral or even increased pre-specified clinical endpoints, and some studies resulted in worsening of HF. This review discusses immune mediators involved in the pathogenesis and progression of HF and potential therapeutic applications targeting inflammation in HF. Besides more obvious settings featuring immune activation such as inflammatory or ischaemic cardiomyopathy, the relevance of immune activation in acute or chronic HF of other origins, including volume overload or valvular heart disease, is highlighted. Understanding how cell-specific and molecular mechanisms of the immune response interfere with cardiac remodelling in HF may open new avenues to design biomarkers or druggable targets.

August 2019 at a glance: arrhythmogenic cardiomyopathy, biomarkers of inflammation, insulin treatment, initiation of sacubitril/valsartan, and pharmacy‐based intervention to increase medication adherence

“…Inflammation has a central role in the pathophysiology of heart failure (HF) . Interleukin (IL)‐6 is an important inflammatory mediator and might constitute a potential pharmacologic target in HF.…”

“…Inflammation has a central role in the pathophysiology of heart failure (HF). 3 Interleukin (IL)-6 is an important inflammatory mediator and might constitute a potential pharmacologic target in HF. IL-6 was measured in patients from the A systems BIOlogy Study to TAilored Treatment in Chronic HF (BIOSTAT-CHF) cohort.…”

Acquired Immunity Is Not Essential for Radiation-Induced Heart Dysfunction but Exerts a Complex Impact on Injury

“…Damage to these and other cell populations can release "danger signals" that trigger inflammatory processes and activate immune cells [18,19]. Inflammation, however, can also contribute to heart homeostasis by promoting tissue remodeling and removing damaged tissue from sites of injury [20,21]. Further complicating this picture, RT can directly affect immune cells, with the effects of cardiac radiation varying dramatically between cell types.…”

Myocardial expression of the anaphylatoxin receptor C3aR is associated with cardiac inflammation and prognosis in patients with non‐ischaemic heart failure

“…Despite some advances in diagnosis and therapy, the prognosis in patients with non‐ischaemic cardiomyopathy remains poor. Chronic low‐grade activation of the innate immune system with increased levels of inflammatory proteins, cytokines, and chemokines has been described in patients with HF . While it has been reported that activation of the immune system is associated with beneficial effects during cardiac regeneration, long‐term immune activation is also known to promote myocardial inflammation, which causes cardiac fibrosis and, thus, progression of HF .…”

“…Chronic low-grade activation of the innate immune system with increased levels of inflammatory proteins, cytokines, and chemokines has been described in patients with HF. [3][4][5][6] While it has been reported that activation of the immune system is associated with beneficial effects during cardiac regeneration, 5,6 long-term immune activation is also known to promote myocardial inflammation, which causes cardiac fibrosis and, thus, progression of HF. 7 Among other mechanisms, infiltration with inflammatory cells mediates an increase of pro-inflammatory proteins in the myocardial tissue followed by myofibroblast activation, accumulation of extracellular matrix proteins, and cardiac remodelling.…”