Kanhai Danny A, de Kleijn Dominique P V, Kappelle L Jaap, Uiterwaal Cuno S P M, van der Graaf Yolanda, Pasterkamp Gerard, Geerlings Mirjam I, Visseren Frank L J
Department of Vascular Medicine, University Medical Center Utrecht (UMC Utrecht), Utrecht, The Netherlands.
BMJ Open. 2014 Jan 14;4(1):e003824. doi: 10.1136/bmjopen-2013-003824.
Extracellular vesicles (EVs) and their protein levels have been identified as a potential risk marker for the development of vascular disease. In the present study, we assessed whether levels of four previously identified EV proteins (cystatin C, serpin G1, serpin F2 and CD14) are associated with cerebral white matter lesions (WMLs) and brain atrophy.
Cohort study; cross-sectional and prospective.
Single centre, secondary and tertiary setting.
1309 patients with manifest vascular disease from the Second Manifestations of ARTerial disease-MR (SMART-MR) study, of which 994 had successful brain MRI and EV protein level measurements.
WML and brain parenchymal fraction (BPF), as parameter for brain atrophy, at baseline and follow-up.
The relationship between EV protein levels and WML volume (expressed as log transformed percentage of intracranial volume) and BPF (expressed percentage of intracranial volume) on 1.5 T brain MRI was assessed with multivariable linear regression modelling. Subsequently, the relationship between baseline EV protein levels and progression of atrophy and WML was analysed in 534 patients, in whom a follow-up MRI was obtained after 4 years.
Higher EV-cystatin C and EV-CD14 were significantly associated with larger WML volume (linear regression coefficient (95% CI) 0.10 log %/SD (0.04 to 0.17) and 0.14 log %/SD (0.07 to 0.20), respectively. Higher EV-CD14 was associated with more brain atrophy (-0.14%/SD; -0.27 to -0.01). Baseline EV-CD14 was significantly associated with increase of WMLs (0.11 log %/SD (0.04 to 0.18)). No relationship with EV-serpins was observed at baseline or at follow-up.
EV proteins cystatin C and CD14 are related to cerebral WMLs and the progression of brain atrophy in patients with manifest vascular disease, potentially identifying EVs in the aetiology of structural brain changes.
细胞外囊泡（EVs）及其蛋白质水平已被确定为血管疾病发生的潜在风险标志物。在本研究中，我们评估了四种先前确定的EV蛋白（胱抑素C、丝氨酸蛋白酶抑制剂G1、丝氨酸蛋白酶抑制剂F2和CD14）的水平是否与脑白质病变（WMLs）和脑萎缩相关。
队列研究；横断面研究和前瞻性研究。
单中心，二级和三级医疗机构。
来自动脉疾病第二次表现-MR（SMART-MR）研究的1309例有明显血管疾病的患者，其中994例成功进行了脑部MRI和EV蛋白水平测量。
WML和脑实质分数（BPF），作为脑萎缩的参数，在基线和随访时进行评估。
采用多变量线性回归模型评估1.5T脑部MRI上EV蛋白水平与WML体积（以颅内体积的对数转换百分比表示）和BPF（以颅内体积的百分比表示）之间的关系。随后，在534例患者中分析了基线EV蛋白水平与萎缩和WML进展之间的关系，这些患者在4年后进行了随访MRI检查。
较高的EV-胱抑素C和EV-CD14与较大的WML体积显著相关（线性回归系数（95%CI）分别为0.10 log%/SD（0.04至0.17）和0.14 log%/SD（0.07至0.20））。较高的EV-CD14与更多的脑萎缩相关（-0.14%/SD；-0.27至-0.01）。基线EV-CD14与WMLs的增加显著相关（0.11 log%/SD（0.04至0.18））。在基线或随访时未观察到与EV-丝氨酸蛋白酶抑制剂的关系。
EV蛋白胱抑素C和CD14与有明显血管疾病患者的脑WMLs和脑萎缩进展相关，可能在脑结构改变的病因中识别出EVs。
