Wang Chao-Hung, Hsieh I-Chang, Cherng Wen-Jin, Chen Chun-Chi, Tung Tao-Hsin, Lee Ju-Fang, Lin Shing-Jong, Wang Po-Nan
Heart Failure Center, Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, 222 Mai Chin Road, Keelung, Taiwan.
Heart Vessels. 2012 Jan;27(1):10-9. doi: 10.1007/s00380-011-0118-4. Epub 2011 Feb 18.
In-stent restenosis is largely due to intimal hyperplasia (IH). The number of vascular progenitor cells (VPCs) mobilized at the acute phase after stenting is associated with IH. This study sought to determine whether the differentiation profile of VPC predicts the development of IH. Peripheral blood was collected in 58 patients after bare-metal stenting to culture VPCs. Intravascular ultrasound was performed to estimate the area of IH 6 months after stenting. VPC differentiation was determined using flow cytometry. VE-cadherin (VE-Cad) and α-smooth muscle actin (α-SMA) were used to identify endothelial and smooth muscle cell lineages, respectively. After culturing, VPCs differentiated into four different phenotypes (α-SMA(-)VE-Cad(+), α-SMA(+)VE-cad(high), α-SMA(+)VE-cad(low), and α-SMA(+)VE-Cad(-)). IH was correlated with gender (P = 0.04), smoking status (P = 0.04), reference diameter (P = 0.03), minimal lumen diameter (P = 0.03), stent area (P < 0.0001), and parameters in the VPC differentiation profile (P < 0.05). Multivariate analysis controlling for stent area, smoking status, and gender revealed that IH was positively and independently associated with the number of differentiated α-SMA(+)VE-Cad (low/-) VPCs (P < 0.0001), and the ratio of α-SMA(+)VE-Cad (low/-) VPCs to α-SMA(-)VE-Cad(+) VPCs (P = 0.001). These parameters in the VPC differentiation profile independently predicted the IH and provided additive information to traditional risk factors. In conclusion, the profile of VPC differentiation predicts the severity of post-stent IH and may be a potential tool in the future for clinicians to identify patients at risk of post-stent restenosis.
支架内再狭窄主要归因于内膜增生（IH）。支架置入急性期动员的血管祖细胞（VPC）数量与IH相关。本研究旨在确定VPC的分化谱是否可预测IH的发生。收集58例接受裸金属支架置入术患者的外周血以培养VPC。在支架置入后6个月进行血管内超声检查以评估IH面积。使用流式细胞术确定VPC分化情况。分别使用血管内皮钙黏蛋白（VE-Cad）和α-平滑肌肌动蛋白（α-SMA）鉴定内皮细胞和平滑肌细胞谱系。培养后，VPC分化为四种不同表型（α-SMA(-)VE-Cad(+)、α-SMA(+)VE-cad(高)、α-SMA(+)VE-cad(低)和α-SMA(+)VE-Cad(-)）。IH与性别（P = 0.04）、吸烟状况（P = 0.04）、参考直径（P = 0.03）、最小管腔直径（P = 0.03）、支架面积（P < 0.0001）以及VPC分化谱中的参数（P < 0.05）相关。在控制支架面积、吸烟状况和性别的多变量分析中，发现IH与分化的α-SMA(+)VE-Cad（低/-）VPC数量呈正相关且独立相关（P < 0.0001），以及α-SMA(+)VE-Cad（低/-）VPC与α-SMA(-)VE-Cad(+) VPC的比例（P = 0.001）。VPC分化谱中的这些参数可独立预测IH，并为传统危险因素提供附加信息。总之，VPC分化谱可预测支架置入后IH的严重程度，未来可能成为临床医生识别支架置入后再狭窄风险患者的潜在工具。
