ABSTRACT
Monocytes are key players in atherosclerotic. Human monocytes display a considerable heterogeneity and at least three subsets can be distinguished. While the role of monocyte subset heterogeneity has already been well investigated in coronary artery disease (CAD), the knowledge about monocytes and their heterogeneity in peripheral artery occlusive disease (PAOD) still is limited. Therefore, we aimed to investigate monocyte subset heterogeneity in patients with PAOD. Peripheral blood was obtained from 143 patients suffering from PAOD (Rutherford stage I to VI) and three monocyte subsets were identified by flow cytometry: CD14++CD16- classical monocytes, CD14+CD16++ non-classical monocytes and CD14++CD16+ intermediate monocytes. Additionally the expression of distinct surface markers (CD106, CD162 and myeloperoxidase MPO) was analyzed. Proportions of CD14++CD16+ intermediate monocyte levels were significantly increased in advanced stages of PAOD, while classical and non-classical monocytes displayed no such trend. Moreover, CD162 and MPO expression increased significantly in intermediate monocyte subsets in advanced disease stages. Likewise, increased CD162 and MPO expression was noted in CD14++CD16- classical monocytes. These data suggest substantial dynamics in monocyte subset distributions and phenotypes in different stages of PAOD, which can either serve as biomarkers or as potential therapeutic targets to decrease the inflammatory burden in advanced stages of atherosclerosis.
Subject(s)
Lipopolysaccharide Receptors/metabolism , Monocytes/cytology , Peripheral Arterial Disease/metabolism , Receptors, IgG/metabolism , Adult , Aged , Aged, 80 and over , Atherosclerosis/metabolism , Body Mass Index , Female , Flow Cytometry , GPI-Linked Proteins/metabolism , Humans , Inflammation , Male , Membrane Glycoproteins/metabolism , Middle Aged , Peroxidase/metabolism , Phenotype , Prospective StudiesABSTRACT
BACKGROUND AND AIMS: We aimed at studying the association of three major human monocyte subsets after percutaneous transluminal angioplasty (PTA) in patients with femoropopliteal disease. METHODS: We prospectively studied 67 sequential patients (40 male, 27 female; mean age 71 ± 11 years) treated with femoropopliteal angioplasty. Multi-color flow cytometry characterized monocyte subsets from venous blood for expression of CD14 and CD16 and intracellular myeloperoxidase (MPO) prior to, and 3, 6 and 12 months post PTA. Analyses tested associations between monocyte subsets and risk for restenosis. RESULTS: 16/67 patients (24%) developed restenosis within 12 months after PTA. Patients with hyperlipidemia had increased risk for restenosis (HR = 1.7, 95% CI 0.7-2.9, p = 0.001). Increased baseline monocytes associated with an increased risk of late restenosis (HR = 4.9, 95% CI: 1.3-18.6, p = 0.047). CD14++CD16++ 'intermediate' monocytes assessed at baseline, and after 3, 6, and 12 months significantly associated with the risk for subsequent restenosis: HR = 3.9 (95% CI: 2.4-6.5, p = 0.029), HR = 5.7 (95% CI = 0.7-44.7, p = 0.013), HR = 6.5 (95% CI: 2.5-16.9, p = 0.001) and HR = 1.5 (95% CI = 1.4-15.5 p = 0.001), respectively. Moreover, the probability for freedom of restenosis decreased with increased levels of intermediate subsets at 12 months after PTA. Additionally, intracellular MPO expression in CD14++CD16++ measured at 3, 6 and 12 months associated with an increased restenosis risk (HR = 1.5, 95% CI: 0.8-2.1, p = 0.214, HR = 1.9, 95% CI: 1.0-2.3 p = 0.051 and HR = 1.4, 95% CI: 1.0-1.8, p = 0.052). CONCLUSIONS: Our results imply altered innate immunity after angioplasty. Elevated CD14++CD16++ intermediate monocyte frequencies and increased MPO expression may identify individuals at heightened risk for restenosis.
