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Acute myocardial infarction (MI) results in tissue damage to affected areas of the myocardium. The initial inflammatory response is the most damaging for residual cardiac function, while at later stages inflammation is a prerequisite for proper healing and scar formation. Balancing the extent and duration of inflammation during various stages after MI is thus pivotal for preserving cardiac function. Recently, a signaling lymphocytic activation molecule 1 (SLAMF1)-derived peptide (P7) was shown to reduce the secretion of inflammatory cytokines and protected against acute lipopolysaccharide-induced death in mice. In the present study, we experimentally induced MI by permanent ligation of the left anterior descending artery (LAD) in mice and explored the beneficial effect of immediately administering P7, with the aim of dampening the initial inflammatory phase without compromising the healing and remodeling phase. Blood samples taken 9 h post-LAD surgery and P7 administration dampened the secretion of inflammatory cytokines, but this dampening effect of P7 was diminished after 3 days. Echocardiography revealed less deterioration of cardiac contraction in mice receiving P7. In line with this, less myocardial damage was observed histologically in P7-treated mice. In conclusion, the administration of a SLAMF1-derived peptide (P7) immediately after induction of MI reduces the initial myocardial inflammation, reduces infarct expansion, and leads to less deterioration of cardiac contraction.

ObjectiveDysregulation of the complement system has been described in patients with heart failure (HF). However, data on the alternative pathway are scarce and it is unknown if levels of factor B (FB) and the C3 convertase C3bBbP are elevated in these patients. We hypothesized that plasma levels of FB and C3bBbP would be associated with disease severity and survival in patients with HF.MethodsWe analyzed plasma levels of FB, C3bBbP, and terminal C5b-9 complement complex (TCC) in 343 HF patients and 27 healthy controls.ResultsCompared with controls, patients with HF had elevated levels of circulating FB (1.6-fold, p < 0.001) and C3bBbP (1.3-fold, p < 0.001). In contrast, TCC, reflecting the terminal pathway, was not significantly increased (p = 0.15 vs controls). FB was associated with NT-proBNP, troponin, eGFR, and i.e., C-reactive protein. FB, C3bBbP and TCC were not associated with mortality in HF during a mean follow up of 4.3 years.ConclusionOur findings suggest that in patients with HF, the alternative pathway is activated. However, this is not accompanied by activation of the terminal pathway.

Background: Obesity is an increasingly prevalent metabolic disorder in the modern world and is associated with structural and functional changes in the heart. The NLRP3 inflammasome is an innate immune sensor that can be activated in response to endogenous danger signals and triggers activation of interleukin (IL)-1β and IL-18. Increasing evidence points to the involvement of the NLRP3 inflammasome in obesity-induced inflammation and insulin resistance, and we hypothesized that it also could play a role in the development of obesity induced cardiac alterations.Methods and Results: WT, Nlrp3−/−, and ASC−/− (Pycard−/−) male mice were exposed to high fat diet (HFD; 60 cal% fat) or control diet for 52 weeks. Cardiac structure and function were evaluated by echocardiography and magnetic resonance imaging, respectively. Whereas, NLRP3 and ASC deficiency did not affect the cardiac hypertrophic response to obesity, it was preventive against left ventricle concentric remodeling and impairment of diastolic function. Furthermore, whereas NLRP3 and ASC deficiency attenuated systemic inflammation in HFD fed mice; long-term HFD did not induce significant cardiac fibrosis or inflammation, suggesting that the beneficial effects of NLRP3 inflammasome deficiency on myocardial remodeling at least partly reflect systemic mechanisms. Nlrp3 and ASC (Pycard) deficient mice were also protected against obesity-induced systemic metabolic dysregulation, as well as lipid accumulation and impaired insulin signaling in hepatic and cardiac tissues.Conclusions: Our data indicate that the NLRP3 inflammasome modulates cardiac concentric remodeling in obesity through effects on systemic inflammation and metabolic disturbances, with effect on insulin signaling as a potential mediator within the myocardium.