Inflammation and Heart Failure: Searching for the Enemy-Reaching the Entelechy

Abstract

The pivotal role of inflammation in the pathophysiology of heart-failure (HF) development and progression has long been recognized. High blood levels of pro-inflammatory and inflammatory markers are present and associated with adverse outcomes in patients with HF. In addition, there seems to be an interrelation between inflammation and neurohormonal activation, the cornerstone of HF pathophysiology and management. However, clinical trials involving anti-inflammatory agents have shown inconclusive or even contradictory results in improving HF outcomes. In the present review, we try to shed some light on the reciprocal relationship between inflammation and HF in an attempt to identify the central regulating factors, such as inflammatory cells and soluble mediators and the related inflammatory pathways as potential therapeutic targets.

Keywords: autoimmunity; heart failure; homeostasis; inflammasome; inflammation; pathophysiology.

Figure 1

Myocardial inflammatory response to an insult (RAAS—renin-angiotensin-aldosterone system; SNS—sympathetic nervous system; ROS—reactive oxygen species).

Figure 2

Mechanisms and mediators involved in the inflammatory process (PRRs—pattern recognition receptors; PAMPs—pathogen associated molecular patterns; DAMPs—damage-associated molecular patterns).

Figure 3

Mechanisms and mediators involved in sterile inflammation (DAMP—damage-associated molecular patterns, TLRs—Toll-like receptors; NF-kB—nuclear factor kappa-beta; NLRs—NOD-like receptors; IL—interleukin).

Figure 4

Deranged homeostasis leading to heart failure.