University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, B18 7QH, UK.
Thromb Haemost. 2013 Jul;110(1):92-100. doi: 10.1160/TH13-02-0088. Epub 2013 Jun 6.
The objective of this study was to evaluate the expression of cell adhesion molecule (CAM) receptors (integrins) on monocyte subsets in heart failure (HF) and examine their prognostic implication.Increased levels of soluble CAMs have been observed in patients with HF, but the precise mechanism of monocyte adhesion to the vascular endothelium remains unknown. Patients with acute HF (AHF, n=51) were compared to those with stable HF (SHF, n=42) and stable coronary artery disease (CAD, n=44) without HF. Expression of integrins-receptors to intercellular adhesion molecule-1 (ICAM-1R) and vascular CAM-1 (VCAM-1R) on monocyte subsets was assessed by flow cytometry. Monocyte subsets were defined as CD14++CD16-CCR2+ ('classical', Mon1), CD14++CD16+CCR2+ ('intermediate', Mon2), and CD14+CD16++CCR2- ('non-classical', Mon3). Compared to patients with SHF, those with AHF had significantly higher expression of ICAM-1R on Mon2 (p=0.01). Compared to those with stable CAD, patients with SHF had a significantly higher expression of ICAM-1R on Mon2 (p=0.025).Compared to SHF, patients with AHF had a similar expression of VCAM-1R on both Mon1 and Mon3 but significantly higher expression on Mon2 (p=0.019). There were no significant differences between SHF and CAD in monocyte expression of VCAM-1R. In multivariate Cox regression analysis, VCAM-1R expression on Mon2 was associated with adverse clinical outcome (death or rehospitalisation) in AHF [HR 1.07 (1.01-1.14), p=0.029]. In conclusion, HF is associated with increased monocyte expression of integrins-receptors to both ICAM-1 and VCAM-1, being particularly linked to Mon2 subset. Expression of VCAM-1R on Mon2 may have prognostic value in patients with AHF.
本研究旨在评估细胞黏附分子 (CAM) 受体(整合素)在心力衰竭 (HF) 患者单核细胞亚群中的表达,并探讨其预后意义。已有研究观察到 HF 患者可溶性 CAM 水平升高,但单核细胞黏附血管内皮的确切机制尚不清楚。本研究比较了急性 HF (AHF, n=51) 患者与稳定 HF (SHF, n=42) 和稳定冠心病 (CAD, n=44) 患者之间的差异。通过流式细胞术评估单核细胞亚群中整合素-细胞间黏附分子-1 (ICAM-1R) 和血管黏附分子-1 (VCAM-1R) 受体的表达。单核细胞亚群定义为 CD14++CD16-CCR2+(“经典”,Mon1)、CD14++CD16+CCR2+(“中间”,Mon2)和 CD14+CD16++CCR2-(“非经典”,Mon3)。与 SHF 患者相比,AHF 患者 Mon2 上的 ICAM-1R 表达显著更高(p=0.01)。与稳定 CAD 患者相比,SHF 患者 Mon2 上的 ICAM-1R 表达显著更高(p=0.025)。与 SHF 相比,AHF 患者 Mon1 和 Mon3 上的 VCAM-1R 表达相似,但 Mon2 上的表达显著更高(p=0.019)。SHF 和 CAD 患者之间,Mon3 上 VCAM-1R 的表达无显著差异。多变量 Cox 回归分析显示,Mon2 上的 VCAM-1R 表达与 AHF 患者不良临床结局(死亡或再住院)相关[风险比 1.07(1.01-1.14),p=0.029]。综上所述,HF 与 ICAM-1 和 VCAM-1 相关整合素受体在单核细胞中的表达增加有关,尤其是与 Mon2 亚群相关。Mon2 上的 VCAM-1R 表达可能对 AHF 患者具有预后价值。