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Objective:To investigate the predictive value of plasma exosomal microRNA (miR)-124-3p in the risk of chronic cerebral hypoperfusion (CCH).Methods:A case-control study. Thirty patients who were diagnosed with CCH (CCH group) based on cranial artery spin labeling (ASL) in the neurology outpatient clinic of Sichuan Provincial People′s Hospital from March 2022 to June 2022 and 30 healthy volunteers (control group) were included. Age, gender, smoking history, alcohol consumption history, diabetes history, hypertension, hyperlipidemia history, uric acid, fasting blood glucose, homocysteine and plasma exosomal miR-124-3p expression level were compared between the two groups. Comparisons of categorical variables were analyzed by either χ2 test or Fisher′s exact test. If the data of continuous variables followed a normal distribution, they were expressed as mean±standard deviation (SD) and compared by t-test for two independent samples; otherwise, the data were expressed as M( Q1, Q3), and analyzed by Mann-Whitney U test for comparison between two groups. The correlation between cerebral blood flow and exosomal miR-124-3p levels was analyzed by Pearson′s correlation. Binary multifactorial logistic regression analysis was used to determine the risk factors associated with CCH, and corresponding odds ratios ( OR) and 95% confidence intervals ( CI) were calculated. P<0.05 was considered significant. Results:There was no significant difference in age (64±8 vs. 60±8 years old), gender (33.3% vs. 30.0%), history of smoking (20.0% vs. 3.3%), alcohol consumption (20.0% vs. 6.7%), diabetes mellitus (13.3% vs. 13.3%), hypertension (53.3% vs. 30.0%), history of hyperlipidemia (46.7% vs. 36.7%), uric acid (288±60 vs.319±67 μmol/L), and fasting glucose [4.99(4.63, 5.91) vs. 5.28(5.09, 6.05) mmol/L] and homocysteine [11.35(10.18, 13.08) vs.11.00(9.78, 13.03) μmol/L] between the CCH and control groups ( P>0.05). Plasma exosomal miR-124-3p expression was significantly higher in the CCH group than in the control group [13.08 (8.59, 21.55) vs. 2.85 (1.44, 5.10), respectively; U=169.50, P<0.001]. Pearson′s correlation test showed that the level of exosomal miR-124-3p was negatively correlated with cerebral blood flow in the hypoperfused region in patients with CCH ( r=-0.932, P<0.001). Multi-factor logistic regression analysis showed that plasma exosomal miR-124-3p was independently associated with the risk of CCH ( OR=1.169,95% CI 1.063-1.286, P=0.001). Conclusions:The expression of plasma exosomal miR-124-3p is negatively correlated with cerebral blood flow in areas of low perfusion and is an independent risk factor for CCH. Plasma exosomal miR-124-3p may thus serve as a valid biomarker for CCH risk prediction.
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Objective To investigate the effect of the reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase on Toll-like receptor 4 (TLR4)-mediated proinflammatory phenotype of cultured vascular smooth muscle cells (VSMCs) in mice.Methods NADPH oxidase agonist platelet-derived growth factorBB (PDGF-BB) and inhibitor apocynin were used respectively to treat cultured VSMCs from C57BL/6J and TLR4-/-mice.The fluorescent probe 2',7'-dichlorodihydrofluorescein diacetate was used to detect the reactive oxygen species (ROS) level in VSMCs.An enzyme-linked immunosorbent assay was used to detect the expressions of interleukin (IL)-6,IL-1β,and tumor necrosis factor-α (TNF-α) in VSMCs.Tetrazolium blue staining and Boyden chamber assay were used to detect the proliferation and migration of VSMC.Results The ROS levels were increased in VSMCs both from C57BL/6J and TLR4-/-mice after PDGF-BB treatment,and this could be inhibited by apocynin.PDGF-BB pretreatment significantly upregulated the expressions of IL-6 (52.69 ±3.49 ng/ml vs.35.04 ±2.74 ng/ml; P =0.001),IL-1β (79.68 ±2.33 ng/ml vs.62.38 ±0.54 ng/ml;P=0.000),and TNF-α (218.35± 5.42 ng/mlvs.124.74± 4.59 ng/ml; P=0.000) in VSMCs from C57BL/6J mice,and the abilities of proliferation (1.69 ± 0.53 vs.1.04 ± 0.40; P =0.000) and migration (42.11 ±4.05 vs.1.69 ± 0.53; P =0.000) were increased significantly; apocynin pretreatment significantly inhibit the expressions of IL-6 (42.11 ± 4.05 ng/ml vs.52.69 ± 3.49 ng/ml; P =0.010),IL-1β (67.57 ± 1.36 ng/ml vs.79.68 ±2.33 ng/ml; P =0.000) and TNF-α (156.18 ± 6.98 ng/ml vs.218.35 ± 5.42 ng/ml;P =0.000),as well as proliferation (1.23 ±0.42 vs.1.69 ±0.53; P =0.000) and migration (42.11 ±4.05 vs.52.69 ± 3.49; P =0.000).While there were no significant changes in the expressions of IL-6,IL-1β,and TNF-α in VSMCs from TLR4-/-mice after PDGF-BB and apocynin pretreatment.Conclusions NADPH oxidase-derived ROS involved in the TLR4-mediated VSMC inflammatory phenotype as well as proliferation and migration,which may be the important mechanisms of its influencing on the occurrence and development of atherosclerosis.
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Intracranial atherosclerosis is one of the important causes of ischemic stroke. Because extra- and intracranial arteries have differences in the structure and hemodynamics, the effects of traditional vascular risk factors, including sex, age, hypertension, and diabetes mellitus, on extra-and intracranial atherosclerosis are also different. The early identification of the risk factors for intracranial atherosclerosis has important significance for aggressively preventing and treating intracranial atherosclerosis and reducing the incidence of ischemic stroke. However, many research conclusions aiming at the risk factors and intracranial ng andatherosclerotic correlation are not consistent. This article reviews the research status quo of the risk factors for intracranial atherosclerosis.