Various aspects of inflammation in heart failure

Abstract

Despite significant advances in the prevention and treatment of heart failure (HF), the prognosis in patients who have been hospitalised on at least one occasion due to exacerbation of HF is still poor. Therefore, a better understanding of the underlying pathophysiological mechanisms of HF is crucial in order to achieve better results in the treatment of this clinical syndrome. One of the areas that, for years, has aroused the interest of researchers is the activation of the immune system and the elevated levels of biomarkers of inflammation in patients with both ischaemic and non-ischaemic HF. Additionally, it is intriguing that the level of circulating pro-inflammatory biomarkers correlates with the severity of the disease and prognosis in this group of patients. Unfortunately, clinical trials aimed at assessing interventions to modulate the inflammatory response in HF have been disappointing, and the modulation of the inflammatory response has had either no effect or even a negative effect on the HF prognosis. The article presents a summary of current knowledge on the role of immune system activation and inflammation in the pathogenesis of HF. Understanding the immunological mechanisms pathogenetically associated with left ventricular remodelling and progression of HF may open up new therapeutic possibilities for HF.

Keywords: Biomarkers; Heart failure; Inflammation; Left ventricular remodelling; Micro-RNA.

Fig. 1

Monocyte activation in HF. This figure shows the basic factors stimulating the activation of monocytes in HF and the basic effects of this monocyte activation. Explanation of abbreviations: LPS lipopolysaccharide, MMP matrix metalloproteinases, NO nitric oxide, ICAM intercellular adhesion molecule, VCAM vascular cell adhesion molecule, ROS reactive oxygen species

Fig. 2

The activation and maintenance of inflammation in HF. This figure shows how the two basic patterns of damage to the myocardium (DAMP and PAMP) lead to the activation and maintenance of inflammation within the myocardium, which ultimately leads to HF. Activation by DAMP and/or PAMP TLRs (these are mainly TLR2, TLR3 and TLR4 which are found in abundance in the myocardium) leads to the activation of NF-kB, which is the basic inflammatory activating factor for inflammation. During myocardial ischaemia, NF-kB is a signalling factor for the production of pro-inflammatory cytokines for many types of cells, including those monocytes infiltrating the myocardium. However, later, the cardiomyocytes themselves, thanks to the increased expression of TLR4 present on their surface, act as pro-inflammatory cells in hearts affected by post-infarction damage. Explanation of abbreviations in the main text