Translational research : the journal of laboratory and clinical medicine
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Clinical observation and ex vivo studies have established a strong association between inflammation and postoperative atrial fibrillation (POAF). However, it is unclear whether the inflammatory phenotype is causally linked to this event or is an epiphenomenon, and it is not known which inflammatory meditators may increase susceptibility to POAF. The limitations of available animal models of spontaneous POAF (sPOAF) makes it difficult to select an experimental system. Here, we provide experimental and clinical evidence for mechanistic involvement of interleukin-6 (IL-6) in sPOAF.
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Neutrophil extracellular traps (NETs) have been implicated in the pathogenesis of abdominal aortic aneurysms (AAAs). This study has addressed the notion that NET components might serve as AAA biomarkers or novel targets of AAA therapy. Thus, parameters of neutrophil activation and NET formation were measured in plasma. ⋯ In an angiotensin II - based mouse model of experimental AAA, an inhibitor of histone citrullination was applied to block NET formation and AAA progression. Of note, further growth of an established aneurysm was prevented in mice treated with the NET inhibitor (P = 0.040). In conclusion, histone citrullination represents a promising AAA biomarker and potential therapeutic target to control disease progression.
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Heart failure is one of the leading causes of death worldwide. A stimulated heart undergoes either adaptive physiological hypertrophy, which can maintain a normal heart function, or maladaptive pathological remodeling, which can deteriorate heart function. These 2 kinds of remodeling often co-occur at the early stages of many heart diseases and have important effects on cardiac function. ⋯ Mechanistically, BAG3 overexpression in NRVCs promoted physiological hypertrophy by activating the protein kinase B (AKT)/mammalian (or mechanistic) target of rapamycin (mTOR) pathway. BAG3 knockdown in NRVCs aggravated pathological remodeling through activation of the calcineurin/nuclear factor of activated T cells 2 (NFATc2) pathway. Because BAG3 has a dual role in cardiac remodeling, heart-specific regulation of BAG3 may be an effective therapeutic strategy to protect against deterioration of heart function and heart failure caused by many heart diseases.