Heart failure in old hypertensive rats is accompanied by the increase of neutrophil extracellular traps and myeloid-derived suppressor cells

Abstract

Arterial hypertension (AH) and heart failure (HF) are age-associated conditions usually accompanied by chronic inflammation. Neutrophil extracellular traps (NET) are important during inflammation and left ventricular remodeling but their functions in HF are poorly studied. Myeloid-derived suppressor cells (MDSC) that fulfill anti-inflammatory functions are also not studied during HF. The goal of this work is to evaluate the balance between proinflammatory NET-producing neutrophils and anti-inflammatory MDSC in pathogenesis of AH and HF in elder rats. Wistar and spontaneously hypertensive rats (SHR) aged 5 and 16 months were subjected to cardiodynamic parameters monitoring. NET formation was examined using fluorescence microscopy. MDSC were determined as CD11b/c⁺-His28⁺-RP1^+/low (granulocytic) and CD11b/c⁺-His28⁺-RP1^- (monocytic) cells by flow cytometry. Signs of HF were observed at AH: aged Wistar rats had decreased by 20.4 ± 15.5% ejection fraction (p = 0.006) compared to young ones, and old SHR by 29.4 ± 21% (p = 0.0007). Aged Wistar rats had the level of NET 3.0 times higher (p = 0.03) than young ones; old SHR-2.9 times higher compared to young SHR (p < 0.001). In old SHR the percentage of granulocytic MDSC from the total number of leukocytes in peripheral blood was 3.98 times higher than in young SHR (p = 0.006), and 3.3 times higher than in old Wistar rats (p = 0.01); and monocytic MDSC-4.75 times higher than in young SHR (p = 0.003), and 2.3 times higher than in old Wistar rats (p = 0.04). Here, we show that HF in old rats leads to significant increase of the NET and MDSC amount versus young animals.

Keywords: Aging; Arterial hypertension; Heart failure; Myeloid-derived suppressor cells; Neutrophil extracellular traps.