Plasma microRNA-210 is associated with VEGF-A and EphrinA3 and relates to coronary collateral circulation in patients with coronary heart disease: a cross-sectional study

Abstract

Background: This study explored the interrelationships among vascular endothelial growth factor A (VEGF-A), microRNA-210 (miR-210), and EphrinA3 in the plasma of patients with coronary heart disease (CHD), and their collective influence on coronary collateral circulation (CCC) development.

Methods: We enrolled 253 patients with ≥ 90% stenosis in at least one coronary artery, stratified into good CCC (n = 99) and poor CCC (n = 154) groups according to the Rentrop grading system. Plasma concentrations of miR-210, VEGF-A, and EphrinA3 were quantified via qRT-PCR and ELISA. The associations between these biomarkers and CCC status were evaluated through correlation analysis, multivariate regression, and mediation analysis.

Results: Good CCC patients demonstrated significantly elevated plasma miR-210 (1.936 [1.099-4.118] vs. 1.272 [0.792-2.081], p < 0.001) and VEGF-A levels (3119.655 ± 850.995 vs. 2910.440 ± 713.218 pg/mL, p = 0.038), alongside reduced EphrinA3 levels (529.594 ± 143.037 vs. 584.657 ± 127.182 pg/mL, p = 0.002) compared to poor CCC patients. ROC analysis revealed AUCs of 0.656 (95% CI: 0.589-0.724) for miR-210, 0.563 (95% CI: 0.489-0.638) for VEGF-A, and 0.632 (95% CI: 0.560-0.705) for EphrinA3, which improved to 0.747, 0.696, and 0.744 respectively after adjustment for confounders. In fully adjusted multivariate models, miR-210 maintained a robust positive association with good CCC (OR: 1.558, 95% CI: 1.257-1.931, p < 0.001), with its highest tertile conferring 4.58-fold increased odds compared to the lowest tertile. Conversely, EphrinA3 exhibited a significant negative association (OR: 0.993, 95% CI: 0.990-0.997, p < 0.001), with its highest tertile linked to 79.4% reduced odds of good CCC. VEGF-A showed a modest association (OR: 1.001, p = 0.043). Notably, mediation analysis revealed that miR-210 functions as a pivotal intermediary in pathways connecting both VEGF-A and EphrinA3 to CCC formation, mediating 77.18% and 49.90% of their respective effects.

Conclusions: Plasma miR-210 levels exhibit a strong association with coronary collateral circulation development and represent a promising biomarker for CCC formation in patients with severe coronary stenosis. The influence of VEGF-A and EphrinA3 on CCC formation appears to be predominantly mediated through miR-210, highlighting its central role in coronary collateralization pathways.

Keywords: Collateral circulation; Coronary heart disease; EphrinA3; MicroRNA-210; VEGF-A.

Fig. 1

Flowchart of patient enrollment. CCC, coronary collateral circulation; CABG, Coronary Artery Bypass Grafting; PCI, percutaneous coronary intervention

Fig. 2

Plasma VEGF-A, miR-210 and EphrinA3 and their correlations in patients with CHD. a-c The plasma level of VEGF-A, miR-210 and EphrinA3 in CHD patients. d-f The linear correlation analysis between miR-210 and VEGF-A, miR-210 and EphrinA3, VEGF-A and EphrinA3. CHD, coronary heart disease; CCC, coronary collateral circulation

Fig. 3

Plasma VEGF-A, miR-210, EphrinA3 and collateral formation. a-c The correlation analysis between VEGF-A, miR-210, EphrinA3 and Good CCC. d-f The proportion of good CCC or poor CCC from the lowest tertile to the highest tertile of VEGF-A, miR-210 and EphrinA3. g-i The nonlinear correlation analysis between miR-210, VEGF-A, EphrinA3 and Good CCC. OR, odds ratio; CCC, coronary collateral circulation

Fig. 4

Receiver-operating characteristic curve analysis for identifying Good CCC. a-c ROC curves evaluating the diagnostic performance of VEGF-A, miR-210 and EphrinA3 associated with good CCC. CCC, coronary collateral circulation; ROC, receiver operating characteristic; AUC, area under the curve