Association between circulating levels of miR-29 and postoperative neurological complications in acute type A aortic dissection patients

TL;DR

This study finds that miR-29 levels in the blood can predict neurological complications and mortality in patients undergoing surgery for aortic dissection.

Contribution

The study identifies miR-29b-3p as a novel independent predictor of postoperative neurological complications and mortality in AAD patients.

Findings

miR-29a-5p and miR-29b-3p were the most significantly dysregulated miRNAs in rat hippocampus under DHCA/CPB.

Preoperative miR-29b-3p and postoperative miR-29a-5p are independent predictors of PONC in AAD patients.

A nomogram based on miR-29 levels showed strong discrimination and clinical utility for predicting PONC and mortality.

Abstract

Postoperative neurological complications (PONC), which are associated with substantial morbidity and mortality, represent a prevalent clinical challenge following surgical repair of acute type A aortic dissection (AAD). This study aimed to identify novel biomarkers for the early diagnosis of PONC, facilitating timely clinical intervention.

We established deep hypothermic circulatory arrest (DHCA) rat models, extracted total RNA from the hippocampus of rats (DHCA and control groups), performed microRNA (miRNA) sequencing, screened for differentially expressed genes (DEGs) between the two groups, and analysed their associated biological processes and pathways. A cohort of 95 patients with AAD was included in this study. Comprehensive clinical assessments and a standardized neuropsychological test battery were systematically conducted. Serum miR-29 levels were quantified via reverse transcription quantitative real-time polymerase chain reaction.

Transcriptomic profiling of the rat hippocampus under DHCA/cardiopulmonary bypass (CPB) revealed 31 differentially expressed miRNAs (FC > 1.5, P < 0.05), with miR-29a-5p and miR-29b-3p showing the most significant dysregulation. Functional enrichment analysis revealed that MAPK signalling and cellular junction pathways are involved in blood–brain barrier modulation. To translate these findings clinically, we analysed a cohort of 95 AAD patients. Compared with patients without PONC, those who developed PONC had significantly longer CPB duration [164.00 (137.00–193.00) vs. 140.00 (120.25–161.00) min; P = 0.012], higher preoperative interleukin-6 levels [106.60 (87.80–154.90) vs. 47.00 (35.45–71.73) pg/mL; P < 0.001], and altered miR-29 expression profiles. Multivariate analysis confirmed that preoperative miR-29b-3p (OR = 2.53, 95% CI 1.17–5.47) and postoperative miR-29a-5p (OR = 0.21, 95% CI 0.05–0.96) were independent predictors of PONC. The nomogram demonstrated robust discrimination (AUC = 0.867) and clinical utility (net benefit = 0.23), with 30-day survival analysis revealed an increased risk of mortality associated with miR-29b-3p (P = 0.041).

This study identified dysregulated miR-29 as a key mechanism linked to PONC after CPB/DHCA and validated circulating miR-29b-3p as an independent predictor of PONC and mortality in AAD patients, providing a basis for early risk assessment.

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