Lo Gullo Alberto, Mandraffino Giuseppe, Imbalzano Egidio, Mamone Federica, Aragona Caterina Oriana, D'Ascola Angela, Loddo Saverio, Cinquegrani Antonella, Alibrandi Angela, Mormina Enricomaria, Bagnato Gianfilippo, Lo Gullo Renato, Sardo Maria Adriana, Saitta Antonino
Department of Clinical and Experimental Medicine, University of Messina, Italy.
Clin Exp Rheumatol. 2014 Nov-Dec;32(6):922-9. Epub 2014 Nov 7.
Circulating proangiogenic haematopoietic cells (PHCs), including CD34+ cells, play an important role in endothelial homeostasis. Among PHCs, CD34+ cells are the largest cell population, thus, much of the regenerative/reparative potential of PHCs may be attributed to CD34+ cells. Our aim was to determine the association between inflammation and CD34+ cell number, intracellular levels of reactive oxygen species (ROS) and expression of Toll-like receptor 3 (TLR3) and interleukin 1β (IL-1β), arterial stiffness (AS) indices, and carotid intima-media thickness (cIMT) in patients affected by rheumatoid arthritis (RA).
CD34+ cells were isolated from 24 RA patients and 26 matched controls. ROS levels, TLR3 and IL-1β expression were measured. C-reactive protein (CRP), fibrinogen, AS, and cIMT were also evaluated.
CD34+ count was lower in RA patients as compared to controls. In CD34+ cells from RA patients, ROS, TLR3 and IL-1β expressions were increased compared to controls. In RA patients, we found higher CRP and fibrinogen levels, and higher values of Pulse Wave Velocity (PWV) and Augmentation Index (AIx), both AS indices, and of cIMT. CD34+ cell numbers were inversely correlated with CRP, TLR3, IL-1β, ROS, and AS indices. TLR3 levels were related to CRP, IL-1β, fibrinogen and ROS. IL-1β levels were correlated with expression of CRP, ROS, and PWV.
Inflammatory status in RA is associated with an increased expression of TLR3 and of IL-1β in CD34+ cells, which appear to affect cell number. These new findings suggest a perspective on accelerated atherosclerosis and vascular damage in RA.
循环促血管生成造血细胞(PHCs),包括CD34+细胞,在内皮稳态中起重要作用。在PHCs中,CD34+细胞是最大的细胞群体,因此,PHCs的许多再生/修复潜能可能归因于CD34+细胞。我们的目的是确定类风湿关节炎(RA)患者炎症与CD34+细胞数量、细胞内活性氧(ROS)水平、Toll样受体3(TLR3)和白细胞介素1β(IL-1β)表达、动脉僵硬度(AS)指数以及颈动脉内膜中层厚度(cIMT)之间的关联。
从24例RA患者和26例匹配的对照中分离出CD34+细胞。测量ROS水平、TLR3和IL-1β表达。还评估了C反应蛋白(CRP)、纤维蛋白原、AS和cIMT。
与对照组相比,RA患者的CD34+细胞计数较低。与对照组相比,RA患者CD34+细胞中的ROS、TLR3和IL-1β表达增加。在RA患者中,我们发现CRP和纤维蛋白原水平较高,脉搏波速度(PWV)和增强指数(AIx)这两个AS指数以及cIMT的值也较高。CD34+细胞数量与CRP、TLR3、IL-1β、ROS和AS指数呈负相关。TLR3水平与CRP、IL-1β、纤维蛋白原和ROS相关。IL-1β水平与CRP、ROS和PWV的表达相关。
RA中的炎症状态与CD34+细胞中TLR3和IL-1β表达增加有关,这似乎会影响细胞数量。这些新发现为RA中动脉粥样硬化加速和血管损伤提供了一个新视角。