Monocyte subsets in heart failure
thesisposted on 11.11.2013, 11:13 by Benjamin J. Wrigley
Introduction: Monocytes play important roles in inflammation, thrombosis, angiogenesis and tissue repair and may contribute to the pathophysiology of heart failure (HF). Functional diversity is likely to stem from the presence of three distinct monocyte subsets, defined by flow cytometry (FC) as CD14++CD16-CCR2+ (Mon1), CD14++CD16+CCR2+ (Mon2) and CD14+CD16++CCR2- (Mon3). The aims of this thesis were to study the following parameters in patients with ischaemic HF: 1) monocyte subset numbers, 2) monocyte subset expression of surface receptors for inflammation, angiogenesis, cell adhesion molecules (CAM) and tissue repair, 3) cross-talk between monocytes and platelets in the formation of monocyte-platelet aggregates (MPAs). Methods: Monocyte subsets were analysed by FC on venous blood samples at baseline in 51 patients admitted with acute HF (AHF), 42 with stable HF (SHF), 44 with stable coronary artery disease (CAD) without HF and 40 healthy controls (HC). Plasma levels of inflammatory cytokines were also measured by flow cytometric bead array technology. In AHF, additional longitudinal samples were taken at discharge and 3 months. Results: Compared to CAD controls, patients with SHF had higher counts of Mon2 and MPAs associated with Mon2, alongside increased expression of inflammatory markers and CAM receptors on Mon2. Compared to SHF, those with AHF had higher counts of Mon1, Mon2 and MPAs associated with Mon1 and Mon2. Patients with AHF also had increased expression of angiogenic receptors on Mon1 and increased expression of angiogenic receptors, scavenger receptors and CAM receptors on Mon2. After adjusting for confounders, counts of Mon2, MPAs associated with Mon2 and expression of VCAM-1R on Mon2 were associated with clinical outcomes in AHF. Conclusions: Differences in monocyte subset numbers and cell surface receptor expression are seen in patients with HF. Mon2 appears to have a prognostic role in patients with AHF, however larger studies are required to confirm these findings.