Monocyte subsets in coronary artery disease and their associations with markers of inflammation and fibrinolysis

详细信息    查看全文

• 作者：Eduard Shantsila ; ^{e.shantsila@bham.ac.uk" class="auth_mail} ; ^{shantsila@yandex.com" class="auth_mail} ; Luke D. Tapp ; Benjamin J. Wrigley ; Burak Pamukcu ; Stavros Apostolakis ; Silvia Montoro-Garc&iacute ; a ; Gregory Y.H. Lip
• 关键词：Monocytes ; Monocyte subsets ; Coronary artery disease ; Interleukin-6 receptor
• 刊名：Atherosclerosis
• 出版年：May, 2014
• 年：2014
• 卷：234
• 期：1
• 页码：4-10
• 全文大小：529 K

文摘

Aims

The multiple roles of monocytes in atherogenesis, including inflammation, angiogenesis and repair are attributed to the existence of different monocyte sub-populations. Scarce data are available on changes in phenotype and functional status of human monocyte subsets in patients with coronary artery disease (CAD), especially when monocytes are evaluated as three distinct subsets.

Methods and results

Surface expression of receptors implicated in inflammation, repair and activation status (intracellular IKK尾) of monocyte subsets was assessed by flow cytometry in 53 patients with CAD and compared to 50 age- and sex-matched healthy controls. Monocyte subsets were defined as CD14++CD16鈭扖CR2+ (Mon1), CD14++CD16+CCR2+ (Mon2), and CD14+CD16++CCR2鈭?(Mon3). Plasma levels of inflammatory cytokines (FACSArray) and fibrinolytic factors (ELISA) were measured in CAD. CAD was associated with reduced expression of CD14 on Mon1 (p聽=聽0.02) and Mon3 (p聽=聽0.036), higher expression of IL6 receptor on Mon1 (p聽=聽0.025) and Mon2 (p聽=聽0.015), CXCR4 on Mon1 (p聽=聽0.035) and Mon3 (p聽=聽0.003), and CD34 on all subsets (all p聽<聽0.007). Monocyte CD163 expression correlated negatively with interleukin (IL)-6 levels (p聽<聽0.01 for all subsets). Expression of vascular endothelial growth factor receptor-1 correlated positively with plasminogen activator inhibitor (PAI)-1 antigen levels (r聽=聽0.47, p聽=聽0.006). In聽vitro, monocyte subsets derived from CAD patients showed significantly altered responses to endotoxin stimulation compared to monocytes from healthy controls.

Conclusions

There is a complex interplay between phenotype and activity of monocytes and plasma cytokines and fibrinolytic factors. These findings support the presence of unique roles for the three human monocyte subsets in atherogenesis and CAD pathogenesis.