<p>Associations of Interleukin 10, Matrix Metallopeptidase 9, and Legumain with Blood Pressure Variability and Neurologic Outcomes in Patients with Ischemic Stroke</p>

Abstract

Background Timely diagnosis and treatment are crucial to improve prognosis of ischemic stroke, making exploring factors associated with prognosis essential. Blood pressure variability (BPV) was reported to be associated with neurologic outcome, and basic researches on cardiovascular diseases found abnormal expression patterns of several factors including interleukin 10 (IL-10), matrix metallopeptidase 9 (MMP-9), and legumain which might be related to abnormal BPV but yet to prove in ischemic stroke. The study aimed to investigate whether IL-10, MMP-9, and legumain are associated with BPV and neurologic outcome of patients with ischemic stroke. Patients and Methods Newly diagnosed ischemic stroke patients admitted to the department of neurology, Shidong Hospital of Yangpu District in Shanghai between July 2017 and January 2019 were enrolled. IL-10, MMP-9, and legumain were detected and BPV was assessed within 72 hours after admission. All the patients were followed for neurologic outcomes at discharge and 6 months after admission based on the Modified Rankin Scale (MRS). Correlations of IL-10, MMP-9, and legumain with BPV were examined by Spearman correlation coefficient, and their associations with neurologic outcomes were evaluated by multivariable linear regression. Results A total of 349 patients with ischemic stroke were enrolled with an average age of 72.97±11.47 years. Compared with non-progressive ischemic stroke, patients with progressive ischemic stroke had significantly higher IL-10, MMP-9, and legumain on admission. MMP-9 was found to be positively correlated with BPV while no significant correlation was found for IL-10 and legumain with BPV. MMP-9 was associated with progressive ischemic stroke [β=0.23 (95% CI 0.11–0.35) per SD increase for MRS at discharge, and β=0.32 (95% CI 0.20–0.43) per SD increase for MRS at 6 months after admission]. Conclusion Increased MMP-9 was associated with increased BPV and progressive ischemic stroke for patients with ischemic stroke, which might partially explain the effect of BPV on neurologic outcomes.

Therapeutic gene delivery by mesenchymal stem cell for brain ischemia damage: Focus on molecular mechanisms in ischemic stroke

“…According to earlier research, interleukin (IL)‐10 may be able to control inflammation by lowering the expression of cytokines and preventing receptor activation. Known as a cytokine production inhibitory factor, IL‐10 has been shown to ameliorate vascular disorder, inactivate numerous cells, impair effector functions, and lessen endothelial cell damage 208–211 . As a result, IL‐10 has immunomodulatory effects throughout an inflammatory response and has an anti‐inflammatory role in the inflammatory response following stroke.…”

The Mammalian Cysteine Protease Legumain in Health and Disease

“…In a mouse model mimicking chronic cerebral hypoperfusion, the depletion of legumain improved cognitive impairment by reducing neuroinflammation, as legumain is upregulated and triggers synaptic plasticity impairment and neuroinflammation [114]. In newly diagnosed progressive ischemic stroke patients, circulatory legumain was significantly higher than in patients with nonprogressive ischemic stroke but was not correlated with blood pressure variability and neurological outcome [115]. In addition, it is shown that legumain contributes to the immune responses during stroke by indirectly altering the number of CD74+ cells in the ischemic hemisphere by the modification of molecules involved in immune cell attraction [72].…”

Elevation of neutrophil carcinoembryonic antigen‐related cell adhesion molecule 1 associated with multiple inflammatory mediators was related to different clinical stages in ischemic stroke patients

“…Furthermore, increased serum IL-10 and MMP-9 was observed in patients with IS, among which IL-10 was found to play an important anti-inflammatory role in responding to brain injury. [18][19][20][21] Previous study showed that carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) played a crucial role in the immune regulation. 22,23 As a member of the immunoglobulin superfamily, CEACAM1 is known as an inhibitory immune co-receptor suppressing the signal transmission via two immunreceptor tyrosine-based inhibition motifs.…”

“…In the previous study, MMP‐9 was considered to play an important role in the BBB injury after IS, while the MMP‐9 inhibitor provided protection against potential alternations in BBB permeability. Furthermore, increased serum IL‐10 and MMP‐9 was observed in patients with IS, among which IL‐10 was found to play an important anti‐inflammatory role in responding to brain injury 18–21 . Previous study showed that carcinoembryonic antigen‐related cell adhesion molecule 1 (CEACAM1) played a crucial role in the immune regulation 22,23 .…”