Key inflammatory mechanisms underlying heart failure

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. 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