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BackgroundAge and sex are prominent risk factors for heart failure and determinants of structural and functional changes of the heart. Cardiac fibroblasts (cFB) are beyond their task as extracellular matrix-producing cells further recognized as inflammation-supporting cells. The present study aimed to evaluate the impact of sex and age on the inflammatory potential of cFB and its impact on the cardiosplenic axis and cardiac fibrosis.MaterialsLeft ventricles (LV) of 3- and 12-months old male and female C57BL/6J mice were harvested for immunohistochemistry, immunofluorescence and cFB outgrowth culture and the spleen for flow cytometry. LV-derived cFB and respective supernatants were characterized.ResultsLV-derived cFB from 3-months old male mice exhibited a higher inflammatory capacity, as indicated by a higher gene expression of CC-chemokine ligand (CCL) 2, and CCL7 compared to cFB derived from 3-months old female mice. The resulting higher CCL2/chemokine C-X3-C motif ligand (Cx3CL1) and CCL7/Cx3CL1 protein ratio in cell culture supernatants of 3-months old male vs. female cFB was reflected by a higher migration of Ly6Chigh monocytes towards supernatant from 3-months old male vs. female cFB. In vivo a lower ratio of splenic pro-inflammatory Ly6Chigh to anti-inflammatory Ly6Clow monocytes was found in 3-months old male vs. female mice, suggesting a higher attraction of Ly6Chigh compared to Ly6Clow monocytes towards the heart in male vs. female mice. In agreement, the percentage of pro-inflammatory CD68+ CD206− macrophages was higher in the LV of male vs. female mice at this age, whereas the percentage of anti-inflammatory CD68+ CD206+ macrophages was higher in the LV of 3-months old female mice compared to age-matched male animals. In parallel, the percentage of splenic TGF-β+ cells was higher in both 3- and 12-months old female vs. male mice, as further reflected by the higher pro-fibrotic potential of female vs. male splenocytes at both ages. In addition, female mice displayed a higher total LV collagen content compared to age-matched male mice, whereby collagen content of female cFB was higher compared to male cFB at the age of 12-months.ConclusionAge- and sex-dependent differences in cardiac fibrosis and inflammation are related to age- and sex-dependent variations in the inflammatory properties of cardiac fibroblasts.

Aim. To compare data on the features of spleen macrophage composition in pa­tients with fatal myocardial infarction (MI) and in patients from the control group without cardiovascular disease (CVD).Material and methods. The study included patients with fatal MI (n=30) and control group (n=5) — persons without CVD who died from injuries not compatible with life. Macrophage infiltration of spleen and myocardium fragments taken during autopsy was assessed by immunohistochemistry using macrophage markers CD68, CD163, CD206, stabilin-1.Results. There were following number of cells studied by us in the red pulp (RP) in patients with MI: CD163+, 906 (661; 1101), CD68+, 898 (807; 1049), stabilin-1+, 811 (531; 966), CD206+, 11 (9; 19); control group: CD163+, 400 (315; 513), CD68+, 40 (37; 45), stabilin-1+, 186 (107; 206), CD206+, 80 (70; 84). The content of all cells in the RP in patients with MI was high and prevailed over their number in the control group, while only the CD206+ concentration was inferior in number; in the control group, CD163+ cells predominated (p

Abstract Aim The acute phase of a coxsackievirus 3 (CVB3)‐induced myocarditis involves direct toxic cardiac effects and the systemic activation of the immune system, including the cardiosplenic axis. Consequently, the nucleotide‐binding oligomerization domain‐like receptor pyrin domain‐containing‐3 (NLRP3) inflammasome pathway is activated, which plays a role in disease pathogenesis and progression. The anti‐inflammatory drug colchicine exerts its effects, in part, via reducing NLRP3 activity, and has been shown to improve several cardiac diseases, including acute coronary syndrome and pericarditis. The aim of the present study was to evaluate the potential of colchicine to improve experimental CVB3‐induced myocarditis. Methods and results C57BL6/j mice were intraperitoneally injected with 1 × 105 plaque forming units of CVB3. After 24 h, mice were treated with colchicine (5 μmol/kg body weight) or phosphate‐buffered saline (PBS) via oral gavage (p.o.). Seven days post infection, cardiac function was haemodynamically characterized via conductance catheter measurements. Blood, the left ventricle (LV) and spleen were harvested for subsequent analyses. In vitro experiments on LV‐derived fibroblasts (FB) and HL‐1 cells were performed to further evaluate the anti‐(fibro)inflammatory and anti‐apoptotic effects of colchicine via gene expression analysis, Sirius Red assay, and flow cytometry. CVB3 + colchicine mice displayed improved LV function compared with CVB3 + PBS mice, paralleled by a 4.7‐fold (P