Inflammatory cell death‐related proteins as potential biomarkers in Takotsubo syndrome

Abstract

BackgroundTakotsubo syndrome (TS), triggered by emotional or physical stress, is prevalent in postmenopausal women and is characterized by an acute and usually reversible left ventricular (LV) wall motion abnormalities. Histopathological analyses of TS animal models revealed presence of single cardiomyocyte cell death with features of inflammatory reaction, however the type of cell death in TS and its impact on the course of the disease has not been explained so far.PurposeThe aim of the study was to evaluate the plasma concentration and release dynamics of proteins associated with inflammatory cell death (pyroptosis, necroptosis) and apoptosis in female rat model of TS.Methods9‐weeks old Sprague Dawley rats were ovariectomized and after 3 weeks received an intraperitoneal injection with a single dose of 150 mg/kg isoprenaline (TO group). The control rats were ovariectomized and received an injection of 0.9% NaCl (CO group). Echocardiography and blood collection was performed 6 (TO6h), 12 (TO12h), 24 (TO24h), 72 (TO72h) hours, and 10 (TO10d) days after ISO or NaCl administration. The plasma concentrations of cell death‐related proteins including: interleukin 1 beta (IL1b) and caspase 1 (casp1) involved in pyroptosis, caspase 3 (casp3) in apoptosis, mixed lineage kinase domain like pseudokinase (MLKL), receptor‐interacting serine/threonine‐protein kinase 1 (RIPK1) and calcium/calmodulin‐dependent protein kinase type II delta chain (CAMK2d) in necroptosis were evaluated.ResultsThe echocardiographic examination in TO group revealed several types of left ventricular wall motion abnormalities, including basal, mid‐basal and apical akinesia, as well as a mixed variant. In comparison to the CO group, the median plasma concentration of IL1b was significantly higher in the TO6h (p<0.01), TO12h (p<0.01), TO24h (p<0.05) and TO72h (p<0.001) series. Moreover, when compared to the CO group, the median plasma concentration of CAMK2d was significantly higher in TO6h (p<0.001), TO12h (p<0.001), TO24h (p<0.001), TO72h (p<0.001) and TO10d (p<0.05) series. No significant differences in mean concentrations of casp1, casp3, MLKL and RIPK1 between CO and TO groups were found.ConclusionsSignificant variability of concentration and release dynamics of inflammatory cell death‐related proteins, including pyroptosis and necroptosis, indicates their potential role in pathogenesis of TS and suggests the potential use of them as biomarkers in TS.Support or Funding InformationThe research is funded by “Diamond Grant” from the Polish Ministry of Science and Higher Education (project No. DI2015 003045).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.