Dynamic Change Of Plasma Decorin Following Ischemic Stroke And Its Clinical Significance

【Background and purpose】 Ischemic stroke is the most common clinical cerebrovasculardisease, and its morbidity, mortality, and disability remained high, which seriously threatenedto the public health. Characterized by multi-factors, multi-mechanisms, multi-aspects, thepathophysiology of ischemic stroke is a malignant cascade process. And the process ofcytotoxicity, oxidative stress, inflammatory cascade, the destruction of Blood-Brain-Barrierand the extracellular matrix remolding (ECM) mechanism contributed greatly to the braininjury of ischemic stroke, among which, the extracellular matrix remolding served as aprotective role in term of repairing necrotic neurons and glial cells and degradation ofblood-brain barrier in the later period of pathophysiology of ischemic stroke. A large numberof studies have reported that several molecules in the extracellular matrix played a role in theprocess of destruction and reconstruction of the blood-brain barrier, necrosis and repairing ofneuron and so on, which exerted significant influence in the development and prognosis ofischemic stroke. There is an obvious relationship between the changes of their activities andmicrovascular permeability of brain, collapsing of blood-brain barrier, invasion ofinflammatory cells, and brain edema. As a small proteoglycan containing leucine-rich aminoacids, Decorin (DCN) is an important mediator in the extracellular matrix, and presents uswith plenty of biological effects. In our previous studies, we found that DCN was involved inthe process of extracellular matrix remolding and apoptosis and regeneration of microvascularendothelial cell in the brain through the research of rat whole-genome chips. And in theexperimental research, it also indicated that DCN had a direct effect to other molecules in theECM. However, the previous studies suggested that DCN may be involved in the regulationof collagen fibrillogenesis, ECM remolding, tumor growth and metastasis, angiogenesis, renaland pulmonary fibrosis, and wound healing, the role of DCN in patients with acute ischemicstroke has not been investigated until now. So the aim of this study was to investigate thedynamic changes in plasma Decorin concentration after acute ischemic stroke and itsrelationship with clinical varieties through case-control study and cohort study, and exploreits clinical significance in the prevention and therapy of cerebrovascular diseases.【Methods】Plasma concentrations of Decorin were assessed in patients with acute ischemicstroke and control subjects using ELISA and the dynamic change of levels of Decorin following ischemic stroke: upon admission (1-3d) between3days and one week (3-7d), andbetween7days and2weeks (7-14d) were also investigated. The relationship betweenDecorin concentration and Trial of ORG10172in Acute Stroke Treatment (TOAST) subtypes,severity (NIHSS), outcomes (mRS), recurrent-onset of stroke and the concentration ofMMP-2were evaluated. The predictive value of Decorin and its exertion to the stroke werealso investigated through the analysis of receiver operating characteristic (ROC) curve andlogistic regression.【Results】 The case-control study shows that the concentration of Decorin significantlydecreased in patients with acute ischemic stroke compared to the controls (p <0.01),especially in the large-artery atherosclerosis group. The level of Decorin was stronglycorrelated with MMP-2(r=0.332; p <0.01). And the cohort study shows that Theconcentration of Decorin gradually decreased following the onset of stroke at all differenttime-points (<3days, p <0.05;3-7days, p <0.01; and7-14days, p <0.01) compared to thecontrols. The gradual decrement persists at least the first two weeks. Decorin levels decreasedmore in the patients with poor outcome (mRS3-6) than those with favorable outcome (mRS0-2, p <0.05) at a time-point of3-7days. Decorin was a significantly diagnostic marker toAIS (p <0.01) and its levels <8500pg/mL had a sensitivity and specificity value of acuteischemic stroke of79.4%and62.8%respectively according to the ROC analysis and logisticregression showed that Decorin <8500pg/mL was associated with acute ischemic stroke(OR=4.8;95%CI:2.1-11.1; P<0.01) following adjustment for potential confounders.【Conclusions】 There is a dynamic reduction in the plasma Decorin levels followingischemic stroke according to the case-control study and cohort study, and the decrementpersists at least the first two weeks. The level of Decorin was positively correlated withMMP-2, and the levels were not the same in the different kind of clinical subgroups. So thedynamic reduction of Decorin might indicate that it may involved in the pathophysiologicalprocesses of stroke and played a role in the process of extracellular matrix remolding,necrosis and repairing of neuron and so on. The change of Decorin might serve as adiagnostic and prognostic marker for acute ischemic stroke.