Innate immune receptors in heart failure: Side effect or potential therapeutic target?

Abstract

Heart failure (HF) is a leading cause of mortality and morbidity in western countries and occasions major expenses for public health systems. Although optimal medical treatment is widely available according to current guidelines, the prognosis of patients with HF is still poor. Despite the etiology of the disease, increased systemic or cardiac activation of the innate immune system is well documented in several types of HF. In some cases there is evidence of an association between innate immune activation and clinical outcome of patients with this disease. However, the few large trials conducted with the use of anti-inflammatory medication in HF have not revealed its benefits. Thus, greater understanding of the relationship between alteration in the immune system and development and progression of HF is urgently necessary: prior to designing therapeutic interventions that target pathological inflammatory processes in preventing harmful cardiac effects of immune modulatory therapy. In this regard, relatively recently discovered receptors of the innate immune system, i.e., namely toll-like receptors (TLRs) and nod-like receptors (NLRs)-are the focus of intense cardiovascular research. These receptors are main up-stream regulators of cytokine activation. This review will focus on current knowledge of the role of TLRs and NLRs, as well as on downstream cytokine activation, and will discuss potential therapeutic implications.

Keywords: Heart failure; Innate immune system; Toll-like receptors; Inflammation

Core tip: Heart failure (HF) is a leading cause of morbidity and mortality despite of current medical and interventional treatment. Activation of the innate immune system leading to or contribute to advanced HF is focus of intense and growing research. This review will focus on the role of innate immune receptors in HF. We will discuss the current knowledge about the correlation of innate immune activation and the clinical course in HF. In addition, we will comment on potential therapeutic implications of modulating the immune system in this syndrome.