Neutrophilic noncoding RNAs predict outcomes of acute ischemic stroke patients treated with recombinant tissue plasminogen activator

Abstract

There’s no evidence demonstrating the association between noncoding RNAs levels before IV recombinant tissue plasminogen activator (rtPA) administration and the outcomes of acute ischemic stroke (AIS). 145 AIS patients received rtPA treatment were recruited at the stroke center from 2018 to 2019, and 103 patients were included in this study. A panel of noncoding RNAs (miRNA-23a, miRNA-193a, miRNA-128, miRNA-99a, miRNA-let-7a, miRNA-494, miRNA-424, and lncRNA H19) were measured in the circulating neutrophils of AIS patients before rtPA treatment. Endpoints included excellent outcome (modified Rankin Scale score [mRS] 0–1) or poor outcome (mRS > 1) at 3 months and symptomatic intracerebral hemorrhage (sICH) after rtPA treatment. Among the eight noncoding RNAs detected in circulating neutrophils of the 103 participants, miRNA-23a levels were associated with the stroke severity on admission and symptom progression at 24 h after rtPA treatment. A noncoding RNA score composed of miRNA-23a, miRNA-99a, and lncRNA H19 was screened to predict the functional outcome at 3 months and the incidence of sICH after rtPA treatment. In the logistic regression analysis, the noncoding RNA score ≥ −0.336 (OR = 2.862 [1.029–7.958], p = 0.044) was an independent predictor of the poor outcome at 3 months after adjustment of clinical variables, the addition of the noncoding RNA score to the clinical model improved the discrimination (IDI% = 4.68 [0.65–8.71], p = 0.020), as well as the net reclassification (NRI% = 33.04 [0.54–71.49], p = 0.016). The noncoding RNA score ≥ −0.336 (OR = 5.250 [1.096–25.135], p = 0.038) was also independently predicted the sICH, the addition of the noncoding RNA score to the clinical variables improved discrimination and reclassification as well. The noncoding RNA score was also associated with the infarct volume and symptom improvement at 7 days after rtPA treatment. In conclusion, a higher neutrophilic noncoding RNA score provides predictive value to identify AIS patients with worse outcomes after rtPA treatment. miRNA-23a, miRNA-99a, and lncRNA H19 are worth further investigation for their effects in thrombolysis after AIS.

Pharmaceutical Strategies to Prevent, Treat, and Recover: Advances and Challenges in Ischemic Stroke and Hemorrhagic Stroke

“…also found that elevated level of H19 expression was associated with the levels of TNF-α, IL-6, IL-1β, ROS, and MDA, showing that H19 was also associated with inflammation and oxidative stress. Also, H19 was found to be associated with the risk of symptomatic ICH in ischemic stroke patients after recombinant tissue plasminogen activator treatment (Han et al, 2022). Collectively, H19 could interact with miRNA and was demonstrated to be associated with NF-κB pathway, inflammation, free radical production and cell death after ICH.…”

“…As mentioned above, after ICH onset, lncRNAs dysregulated not only in brain tissue, but also in the circulation system, such as MEG3 and FGD5-AS1 (Hao et al, 2022;Jiang et al, 2022;. Also, the association between H19 and the risk of symptomatic ICH in ischemic stroke patients treated with recombinant tissue plasminogen activator was established (Han et al, 2022). The presence of dysregulated lncRNAs in serum, which were also associated with ICH, provided an easier sampling routine and opportunities to use lncRNAs as biomarkers in diagnosing ICH.…”

Long non-coding RNAs in intracerebral hemorrhage

“… Mao et al (2022) also found that elevated level of H19 expression was associated with the levels of TNF-α, IL-6, IL-1β, ROS, and MDA, showing that H19 was also associated with inflammation and oxidative stress. Also, H19 was found to be associated with the risk of symptomatic ICH in ischemic stroke patients after recombinant tissue plasminogen activator treatment ( Han et al, 2022 ). Collectively, H19 could interact with miRNA and was demonstrated to be associated with NF-κB pathway, inflammation, free radical production and cell death after ICH.…”

“…As mentioned above, after ICH onset, lncRNAs dysregulated not only in brain tissue, but also in the circulation system, such as MEG3 and FGD5-AS1 ( Hao et al, 2022 ; Jiang et al, 2022 ; Wang H. et al, 2022 ). Also, the association between H19 and the risk of symptomatic ICH in ischemic stroke patients treated with recombinant tissue plasminogen activator was established ( Han et al, 2022 ). The presence of dysregulated lncRNAs in serum, which were also associated with ICH, provided an easier sampling routine and opportunities to use lncRNAs as biomarkers in diagnosing ICH.…”

Circulating miRNA profiles and the risk of hemorrhagic transformation after thrombolytic treatment of acute ischemic stroke: a pilot study

“…In another study, miR-21-5p, miR-206, and miR-3123 were implicated in predicting the risk of hemorrhagic transformation in patients with cardioembolic stroke ( 21 ). Additionally, the assessment of RNA markers, including miRNA-23a, miRNA-193a, miRNA-128, miRNA-99a, miRNA-let-7a, miRNA-494, miRNA-424, and the long non-coding (lnc)RNA H19, has been shown to improve the prediction of symptomatic intracranial hemorrhage (sICH) after rtPA ( 22 ).…”