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Review
. 2019 Apr;44(2):96-106.
doi: 10.1007/s00059-019-4785-8.

Key inflammatory mechanisms underlying heart failure

C Riehle  1 , J Bauersachs  2
Affiliations
Review

Key inflammatory mechanisms underlying heart failure

C Riehle et al. Herz. 2019 Apr.

Abstract
in English, German

Inflammation plays a central role in the development of heart failure, especially in heart failure with preserved ejection fraction (HFpEF). Furthermore, the inflammatory response enables the induction of regenerative processes following acute myocardial injury. Recent studies in humans and animals have greatly advanced our understanding of the underlying mechanisms behind these adaptations. Importantly, inflammation can have both beneficial and detrimental effects, dependent on its extent, localization, and duration. Therefore, modulation of cardiac inflammation has been suggested as an attractive target for the treatment of heart failure, which has been investigated in numerous clinical trials. This review discusses key inflammatory mechanisms contributing to the pathogenesis of heart failure and their potential impact as therapeutic targets.

Entzündungsprozesse spielen eine zentrale Rolle bei der Entwicklung der Herzinsuffizienz, insbesondere bei Herzinsuffizienz mit erhaltener Ejektionsfraktion (HFpEF). Darüber hinaus sind Entzündungsprozesse allerdings auch für die Reparationsvorgänge nach akutem Myokardinfarkt erforderlich. Sowohl aktuelle Studien an Tiermodellen als auch Untersuchungen an Menschen führten zu einem besseren Verständnis der zugrunde liegenden Mechanismen. Abhängig von Lokalisation, Ausmaß und der Dauer können Entzündungsprozesse sowohl vorteilhaft als auch nachteilig sein. Deshalb bietet sich deren Beeinflussung als ein möglicher Angriffspunkt zur Behandlung der Herzinsuffizienz sowie pathologischer Umbauvorgänge an. Dies ist Gegenstand zahlreicher klinischer Studien. In der vorliegenden Übersichtsarbeit wird die Rolle wesentlicher Entzündungsprozesse in der Pathogenese der Herzinsuffizienz erörtert und deren potenzielle Bedeutung als Therapieoption diskutiert.

Keywords: Cardiac failure; Cytokines; Immune system; Inflammation; Myocardial infarction.

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Conflict of interest statement

C. Riehle received travel support from Abiomed. J. Bauersachs received honoraria for lectures and advice from Novartis, Pfizer, Vifor, Bayer, BMS, Servier, AstraZeneca, Orion, CVRx, Abiomed, Abbott, and Medtronic, and research support from Zoll, CVRx, Bayer, Vifor, Abiomed, and Medtronic.

Figures

Fig. 1
Fig. 1
Schematic depicting the impact of endothelial dysfunction and inflammation on the development of fibrosis and heart failure with preserved ejectionfraction (HFpEF). Comorbidities, such as renal failure, arterial hypertension, chronic obstructive pulmonary disease (COPD), metabolic syndrome, diabetes mellitus, and iron deficiency, induce systemic inflammation. Increased mitochondrial reactive oxygen species (ROS) production, increased peroxynitrite (ONOO−) levels, and decreased nitric oxide (NO) levels in endothelial cells attenuate cardiomyocyte soluble guanylate cyclase (sGC)/guanosine monophosphate (cGMP)/protein kinase G (PKG) signaling, which induces adverse left-ventricular remodeling and diastolic dysfunction. Inflammation also promotes fibrosis by differentiation of fibroblasts into myofibroblasts following transforming growth factor beta (TGFβ) secretion by monocytes
Fig. 2
Fig. 2
Time course of inflammation and healing after myocardial infarction in mice. The acute inflammatory response is characterized by infiltration with M1 macrophages (Mɸ1), Ly6Chigh monocytes, and neutrophils. The main characteristics of the healing phase are infiltration with M2 macrophages (Mɸ2), Ly6Clow monocytes and myofibroblasts, which contribute to wound repair, neovascularization, limitation of tissue damage, and reparative fibrosis of the infarct zone. Chronic inflammation might result from persistent inflammation following the healing phase or a second boost of inflammation. Note that the categorization of macrophages into “M1” and “M2” subtypes is an oversimplification and that the different phases require a greater time span in larger animals and humans. LV left-ventricular
See this image and copyright information in PMC

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