Pentraxin-3 regulates the inflammatory activity of macrophages

Background and aims: Pentraxin-3 (PTX3) reportedly has protective roles in atherosclerosis and myocardial infarction, and is a useful biomarker of vascular inflammation. However, the detailed functions of PTX3 in inflammation are yet to be elucidated. This study aimed to investigate the function of PTX3 in macrophages. Methods: PMA-treated THP-1 cell line (THP-1 macrophage) and monocyte-derived human primary macrophages were treated with recombinant PTX3. Cytokine and chemokine levels in the THP-1 culture medium were measured as well as monocyte chemoattractant protein (MCP-1) concentrations in the Raw 264.7 cell culture medium. PTX3-silenced apoptotic macrophages (THP-1 cell line) were generated to investigate the roles of PTX3 in phagocytosis. Results: In the presence of PTX3, macrophage interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α) and MCP-1 levels were reduced significantly (−39%, P=0.007; −21%, P=0.008; and −67%, P=0.0003, respectively), whilst activated transforming growth factor-β (TGF−β) was detected in the THP-1 macrophages (P=0.0004). Additionally, PTX3 induced Akt phosphorylation and reduced nuclear factor-kappa B (NF-κB) activation by 35% (P=0.002), which was induced by TNF-α in THP-1 macrophages. Furthermore, silencing of PTX3 in apoptotic cells resulted in increased macrophage binding, elevated expression rate of HLA-DR (+30%, P=0.015) and CD86 (+204%, P=0.004) positive cells, and induction of IL-1β (+36%, P=0.024) production. Conversely, adding recombinant PTX3 to macrophages reduced CD86 and HLA-DR expression in a dose-dependent manner. Conclusions: We identified PTX3 as a novel regulator of macrophage activity, and this function suggests that PTX3 acts to resolve inflammation

Relationship between Cardiac Acoustic Biomarkers and Pulmonary Artery Pressure in Patients with Heart Failure

Since an elevation of pulmonary artery pressure (PAP) often precedes clinical worsening of heart failure (HF), early and non-invasive detection of this sign is useful in HF care. This study aimed to assess whether cardiac acoustic biomarkers (CABs) are associated with the elevation of PAP in patients with HF. Patients with HF scheduled to undergo right heart catheterization were prospectively enrolled. CABs were concurrently recorded during catheterization at rest (baseline) and while applying a handgrip (exercise). Forty-nine patients were included in the analysis, and their mean PAP significantly increased after exercise compared to baseline. Several CABs correlated significantly with mean PAP by absolute values, among which S2 Width (r = 0.354; p = 0.014 and r = 0.363; p = 0.010) and S3 Strength (r = 0.375; p = 0.009 and r = 0.386; p = 0.007) were consistent throughout baseline and exercise. The response of CABs to exercise-induced PAP elevation was divided into two patterns: increasing and decreasing. The frequency of cardiac index below 2.2 mL/m2 was significantly higher in the decreasing pattern. CABs related to S2 and S3 showed significant correlations with absolute PAP values both at baseline and after exercise in patients with HF, but no significant correlations between their changes from baseline to post-exercise were observed in this study population. Further research is therefore needed to assess whether CABs can sensitively reflect changes in PAP according to HF status and underlying phenotypes