Phenotype Changes of Circulating Monocytes in a Hypercholesterolemic Swine Model of Coronary Artery Disease

Abstract

Objective: Inflammation and immunity activation play a key role in atherosclerosis (ATS) onset and progression. Aim of this study was to investigate the relationships between phenotype of circulating monocytes and coronary artery disease (CAD) development in a histologically well-characterized swine model of ATS. Methods:Blood samples were obtained from 6 animals at baseline and after 16 weeks high fat cholesterolenriched diet. Flow cytometry monocyte identification was performed (CD172a marker). Adhesion (CD18a, CD11a, CD11R3, CD49d, CD29), differentiation (CD14) and activation receptors (SLA-DR, CD16, CD163) were quantified as percentage of positivity (%) and Relative Fluorescence Intensity (RFI). Lipid parameters (LDL, oxLDL, HDL) and soluble endothelial ICAM-1 were measured and histologic quantitative assessment of coronary ATS was performed. Results:Flow cytometry analysis demonstrated a significant post-diet decrease of CD14 RFI and an increment of % SLA-DR. Pre-diet values of ICAM-1 and % SLA-DR correlated reciprocally (P=0.0191) and with several CAD severity indexes (P≤0.02). Positive correlations between RFI changes of CD29 (P=0.0213) and CD18a (P=0.0341) and morphometric indexes of coronary ATS were found. Post-diet RFI values of CD29, CD18a and CD16 were also closely related to morphometric parameters (P<0.03). A cumulative post-diet tendency to increase of CD14 low / CD163 high monocyte fraction (45.07 ± 2.27 vs. 40.14 ± 3.16) and a tight correlation between changes of this monocyte subset and corresponding HDL variations (P=0.0100) were also observed. Conclusions:Blood monocyte orientation towards a macrophage-like phenotype, similar to a HDL-induced maturation, and a close association between markers changes and severity of diet induced coronary ATS could provide new insights into plaque growth and progression in CAD.

Cortical bone stem cells modify cardiac inflammation after myocardial infarction by inducing a novel macrophage phenotype

“…Our examination of day 7 post-MI captures only a narrow slice of the entire wound healing process, and effects of CBSC therapy on cell types like neutrophils and monocytes, which are critical to the immune response to cardiac wound healing, may not be accurately represented looking at this time point. Although the analysis of swine cardiac immune cells by flow cytometry may not yet be commonplace in basic cardiovascular research, all immune cell markers used in this study were taken directly from previously established cell-membrane markers of porcine immune cell populations (71)(72)(73)(74). Lastly, the pig heart is a vast organ compared with a mouse or rat, and although we have taken targeted approaches in our analysis of the infarct, it is not feasible to analyze the pig heart as thoroughly as a mouse or rat heart.…”