Search

Background: Heart failure with reduced (HFrEF) or preserved ejection fraction (HFpEF) is characterized by low-grade chronic inflammation. Circulating neutrophils regroup 2 subtypes termed high- and low-density neutrophils (HDNs and LDNs). LDNs represent less than 2% of total neutrophil under physiological conditions, but their counts increase in multiple pathologies, releasing more inflammatory cytokines and neutrophil extracellular traps (NETs). The aims of this study were to assess the differential count and role of HDNs, LDNs, and NETs-related activities in patients with heart failure (HF)., Methods: HDNs and LDNs were isolated from human blood by density gradient and purified by fluorescence-activated cell sorting (FACS) and their counts obtained by flow cytometry. Formation of NETs (NETosis) was quantified by confocal microscopy. Circulating inflammatory and NETosis biomarkers were measured by enzyme-linked immunosorbent assay (ELISA). Neutrophil adhesion onto human extracellular matrix (hECM) was assessed by optical microscopy., Results: A total of 140 individuals were enrolled, including 33 healthy volunteers (HVs), 41 HFrEF (19 stable patients and 22 presenting acute decompensated HF [ADHF]), and 66 patients with HFpEF (36 stable patients and 30 presenting HF decompensation). HDNs and LDNs counts were significantly increased up to 39% and 2740%, respectively, in patients with HF compared with HVs. In patients with HF, the correlations among LDNs counts and circulating inflammatory (CRP, IL-6 and -8), troponin T, N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and NETosis components were significant. In vitro, LDNs expressed more citrullinated histone H3 (H3Cit) and NETs and were more proadhesive, with ADHFpEF patients presenting the highest proinflammatory profile., Conclusions: Patients with HFpEF present higher levels of circulating LDNs- and NETs-related activities, which are the highest in the context of acute HF decompensation., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Clinical studies have revealed a greater risk of pulmonary autograft dilation after the Ross procedure in patients with preoperative aortic insufficiency (AI). The present study examined whether the morphologic, biomechanical, and cellular properties of the pulmonary artery (PA) from patients with AI were phenotypically different compared with patients diagnosed with aortic stenosis (AS)., Methods: PA segments were harvested from patients undergoing the Ross procedure for AS (n = 16) and AI (n = 6). Preoperative aortic annulus was significantly larger (P < 0.05) in patients with AI (28.5 ± 1.8 mm) vs AS (22.8 ± 1.2 mm). Morphologic, biomechanical, and cellular phenotypes of the PA were analyzed., Results: Collagen and elastin content in the media of the PA wall were similar in patients with AS and AI. Elastic modulus and energy loss of the PA were not significantly different between the groups. In the media of the PA, expression of a panel of vascular smooth muscle cell-specific proteins were similar in patients with AS and AI. In contrast, nonmuscle myosin IIB protein levels in the PA of AS patients were significantly higher compared with AI patients, and immunofluorescence identified staining in α-smooth muscle actin-positive vascular smooth muscle cells., Conclusions: Despite similar morphological and biomechanical properties, the disparate expression of nonmuscle myosin IIB protein distinguishes the PA of patients with AI from patients with AS. The biological role in vascular smooth muscle cells and the potential contribution of nonmuscle myosin IIB to pulmonary autograft dilation in a subset of AI patients after the Ross procedure remain to be determined., (Copyright © 2020 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)