Department of NEUROFARBA, Neuroscience Section, University of Florence, Florence, Italy.
Stroke Unit and Neurology, Careggi University Hospital, Largo Brambilla 3, 50134, Florence, Italy.
Transl Stroke Res. 2019 Feb;10(1):44-51. doi: 10.1007/s12975-018-0627-x. Epub 2018 Apr 23.
Small vessel disease (SVD) is frequent in aging and stroke patients. Inflammation and remodeling of extracellular matrix have been suggested as concurrent mechanisms of SVD. We investigated the relationship between imaging features of SVD and circulating metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in patients with ischaemic stroke. In patients treated with intravenous thrombolysis, we took blood samples before intravenous thrombolysis and 90 days after the acute stroke and analysed levels of MMPs and TIMPs. We assessed leukoaraiosis, number of lacunes and brain atrophy on pre-treatment CT scan and graded global SVD burden combining such features. We investigated associations between single features, global SVD and MMPs and TIMPs at baseline and at follow-up, retaining univariate statistically significant associations in multivariate linear regression analysis and adjusting for clinical confounders. A total of 255 patients [mean (±SD) = 68.6 (± 12.7) years, 154 (59%) males] were included, 107 (42%) had no signs of SVD; 47 (19%) had from moderate to severe SVD burden. A total of 107 (42%) patients had no signs of SVD; 47 (19%) had from moderate to severe SVD burden. After adjustment, only TIMP-4 proved associations with SVD features. Brain atrophy was associated with baseline TIMP-4 (β = 0.20;p = 0.019) and leukoaraiosis with 90 days TIMP-4 (β = 0.19; p = 0.013). Global SVD score was not associated with baseline TIMP-4 levels (β = 0.10; p = 0.072), whereas was associated with 90 days TIMP-4 levels (β = 0.21; p = 0.003). Total SVD burden was associated with higher TIMP-4 levels 90 days after stroke, whereas was not during the acute phase. Our results support a biological relationship between SVD grade and TIMP-4.
小血管疾病（SVD）在衰老和中风患者中很常见。细胞外基质的炎症和重塑被认为是 SVD 的并发机制。我们研究了缺血性中风患者 SVD 的影像学特征与循环金属蛋白酶（MMPs）和金属蛋白酶组织抑制剂（TIMPs）之间的关系。在接受静脉溶栓治疗的患者中，我们在静脉溶栓前和急性中风后 90 天采集血液样本，并分析 MMPs 和 TIMPs 的水平。我们在治疗前 CT 扫描上评估了脑白质疏松症、腔隙数量和脑萎缩，并结合这些特征对 SVD 总负荷进行分级。我们研究了基线和随访时单个特征、总体 SVD 与 MMPs 和 TIMPs 之间的相关性，保留多元线性回归分析中具有统计学意义的单变量相关性，并调整临床混杂因素。共纳入 255 例患者[平均（±标准差）=68.6（±12.7）岁，154 例（59%）男性]，107 例（42%）无 SVD 征象；47 例（19%）有中至重度 SVD 负荷。共有 107 例（42%）患者无 SVD 征象；47 例（19%）有中至重度 SVD 负荷。调整后，只有 TIMP-4 与 SVD 特征呈显著相关。脑萎缩与基线 TIMP-4 相关（β=0.20;p=0.019），脑白质疏松症与 90 天后 TIMP-4 相关（β=0.19;p=0.013）。SVD 总评分与基线 TIMP-4 水平无关（β=0.10;p=0.072），但与 90 天后 TIMP-4 水平相关（β=0.21;p=0.003）。SVD 总负荷与中风后 90 天 TIMP-4 水平升高相关，而在急性期则无相关性。我们的研究结果支持 SVD 分级与 TIMP-4 之间存在生物学关系。
