Association of the TREM‐1–STAT3 Axis With Stroke Severity and Functional Outcomes in Ischemic Stroke: A Prospective Case‐Control Study
Haohai Lin, Yan Dong, Zhangping He, Chao Qin, Pingping LiABSTRACT
Background
Information regarding the signaling axis involving triggering receptor expressed on myeloid cells 1 (TREM‐1) and its downstream mediator, signal transducer and activator of transcription 3 (STAT3), remains limited in ischemic stroke. We investigated the plasma levels of TREM‐1 in patients with ischemic stroke and compared to controls. Second, we investigated the potential correlation between plasma TREM‐1 levels and STAT3 expression in peripheral blood mononuclear cells (PBMCs) and explored their associations with stroke severity and functional outcomes.
Methods
In an observational case‐control study, plasma and PBMCs from participants were collected to measure TREM‐1 and STAT3 expression levels. The National Institutes of Health Stroke Scale (NIHSS) at admission, day 7, and 1 and 3 months, and the modified Rankin Scale (mRS) at 3 months post‐discharge were assessed. Plasma TREM‐1 levels and STAT3 expression were measured by enzyme‐linked immunosorbent assay (ELISA) and quantitative reverse transcription polymerase chain reaction (RT‐qPCR), respectively. The Inflammation‐Related Principal Component Score (IRPCS) was examined for its association with 3‐month functional outcome.
Result
TREM‐1 and STAT3 were significantly elevated in acute ischemic stroke (AIS) patients ( p < 0.05, p < 0.0001) and positively correlated (ρ = 0.432, p < 0.0001). Both biomarkers correlated with the NIHSS at 1 and 3 months and mRS at 3 months (all p < 0.05). The composite IRPCS showed the strongest association with poor 3‐month functional outcome among the tested biomarkers (OR = 2.84, 95% CI: 1.32–6.12, p = 0.008).
Conclusion
Plasma TREM‐1 levels were positively correlated with STAT3 expression. The TREM‐1–STAT3 axis was associated with stroke severity and 3‐month functional outcome in AIS patients. These findings should be regarded as exploratory and require validation in larger cohorts.