Associations between Hypertriglyceridemia and Circulating Neutrophil Subpopulation in Patients with Dyslipidemia.

Background: There is strong evidence to suggest that the negative influence of triglyceride-rich lipoproteins (TRLs) on atherosclerosis development and progression is at least partially mediated by their proinflammatory effects. However, the effect of hypertriglyceridemia (HTG) on the subpopulation composition of circulating neutrophils has not been studied so far. The aim of this study was to examine correlations between the level of triglycerides (TGs) and the subpopulation composition of circulating neutrophils in middle-aged patients with dyslipidemia without established atherosclerotic cardiovascular diseases (ASCVDs).

Methods: Ninety-one patients with dyslipidemia, including 22 (24.2%) patients with HTG, were enrolled in the study. Phenotying of neutrophil subpopulations was performed through flow cytometry (Navios 6/2, Beckman Coulter, USA). For phenotyping of neutrophil subpopulations, conjugated monoclonal antibodies were used: CD16, PE-Cyanine7 (Invitrogen, USA); CD11b-FITC (Beckman Coulter, USA); CD62L-PE (Beckman Coulter, USA); and CD184 (CXCR4)-PE-CF594 (BD Biosciences, USA).

Results: Following the correlation analysis, the TG level directly correlated with the number of circulating leukocytes (r = 0.443; p < 0.0001) and neutrophils (r = 0.311; p=0.008). HTG patients displayed a significantly high number of circulating neutrophils with CD16^hiCD11b^hiCD62L^hi and CD16^hiCD11b^loCD62L^br phenotypes. TG levels directly correlated with the number of circulating neutrophils having CD16^hiCD11b^hiCD62L^hi and CD16^hiCD11b^loCD62L^br phenotypes. Following the linear regression analysis, statistically significant correlations between TG levels and neutrophil subpopulations having CD16^hiCD11b^loCD62L^br and CD16^hiCD11b^brCD62L^loCXCR4^hi phenotypes were established. Changes in TG levels could explain up to 19.1% of the variability in the number of studied neutrophil subpopulations.

Conclusion: Among middle-aged patients without established ASCVDs, patients with HTG demonstrated a significantly higher overall number of neutrophils and neutrophils having CD16^hiCD11b^hiCD62L^hi (mature neutrophils) and CD16^hiCD11b^loCD62L^br (immunosuppressive neutrophils) than patients with normal TG levels. The TG level was associated with an increase in the number of CD16^hiCD11b^loCD62L^br and CD16^hiCD11b^brCD62L^loCXCR4^hi (ageing neutrophils) neutrophils, adjusted for the sex and age of the patients.