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Review
. 2022 Dec 15;23(24):15946.
doi: 10.3390/ijms232415946.

Alarmins as a Possible Target of Future Therapies for Atrial Fibrillation

Egidio Imbalzano  1 , Giuseppe Murdaca  2 , Luana Orlando  1 , Marianna Gigliotti-De Fazio  1 , Dario Terranova  1 , Alessandro Tonacci  3 , Sebastiano Gangemi  4
Affiliations
Review

Alarmins as a Possible Target of Future Therapies for Atrial Fibrillation

Egidio Imbalzano et al. Int J Mol Sci. .

Abstract

To date, worldwide, atrial fibrillation is the most common cardiovascular disease in adults, with a prevalence of 2% to 4%. The trigger of the pathophysiological mechanism of arrhythmia includes several factors that sustain and exacerbate the disease. Ectopic electrical conductivity, associated with the resulting atrial mechanical dysfunction, atrial remodeling, and fibrosis, promotes hypo-contractility and blood stasis, involving micro endothelial damage. This causes a significant local inflammatory reaction that feeds and sustains the arrhythmia. In our literature review, we evaluate the role of HMGB1 proteins, heat shock proteins, and S100 in the pathophysiology of atrial fibrillation, offering suggestions for possible new therapeutic strategies. We selected scientific publications on the specific topics "alarmins" and "atrial fibrillation" from PubMed. The nonsystematic review confirms the pivotal role of molecules such as S100 proteins, high-mobility group box-1, and heat shock proteins in the molecular pattern of atrial fibrillation. These results could be considered for new therapeutic opportunities, including inhibition of oxidative stress, evaluation of new anticoagulant drugs with novel therapeutic targets, molecular and genetic studies, and consideration of these alarmins as predictive or prognostic biomarkers of disease onset and severity.

Keywords: HMGB1; S100 protein; alarmins; atrial fibrillation; heat shock proteins.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
HMGB1 appears to be highly represented in patients with atrial fibrillation, correlating its concentration with malondialdehyde (MDA) and C-reactive protein (HS-CRP), which represents another inflammatory protein. HMBG1 could be amplifier of the inflammatory response with the recall of proinflammatory cytokines such as IL-1, tumor necrosis factor (TNF) and IL-6, which handle atrial remodeling, fibrosis and in the onset of post-surgical AF.
Figure 2
Figure 2
S100β is released because of the neuronal injury of the intrinsic cardiac autonomic nervous system (ICSN), which releases other damage-associated molecular pattern proteins (DAMPs). At the same time, the trophic role of S100β is also shown, which, released from glial cells, through the RAGE receptor would be able to regenerate peripheral cardiac nerves.
Figure 3
Figure 3
High levels of HSP70 have been shown in patients with atrial fibrillation as a protective antiarrhythmic molecule, correlating with sIL-2 (green arrow) and inversely correlated with sIL-4 concentration (red arrow).
See this image and copyright information in PMC

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