The microRNAs inhibiting atheroprotective pathways in correlation with atherosclerosis severity in chronic coronary syndrome patients – case control study and network analysis

Atherosclerotic plaque progression is regulated by microRNAs. In addition to atherogenic pathways, there are also factors that inhibit the plaque development at crucial stages - KLF2, KLF4, Mert-K, IL-10 and TGF-β. These factors are downregulated by the following microRNAs – miR-92a downregulates KLF-2, miR-10b – KLF4, miR-126 – Mert-K, miR-98 – IL10 and miR-29b – TGFβ1 and TGFβ3. A total of 44 patients with chronic coronary syndrome and atherosclerotic lesions confirmed by coronary angiography and 10 healthy volunteers were enrolled in the study. Patients were classified according to atherosclerotic burden (assessed by the Gensini Score) and the presence of advanced atherosclerotic lesion in a coronary branch (i.e. significant stenosis or chronic occlusion). The relative expression levels in plasma of miR-92a, miR-10b, miR-126, miR-98 and miR-29b in plasma were measured by quantitative RT-PCR and relations between these particles were also assessed by network analysis. The study showed that patients with the lowest burden of atherosclerosis had significantly increased levels of miR-126 (57.93 ± 6.87 for Gensini tertile 1 vs. 41.60 ± 4.52 for Gensini tertiles 2 and 3 considered as one group, p = 0.0472), whereas patients with advanced atherosclerosis had significantly increased levels of miR-92a − 51.02 [20.56–72.68] vs 94.93 [67.04-133.78], p = 0.0074). Moreover, the network analysis revealed strong positive correlation between miR-92a and miR-98, miR-10b and miR-126 as well as miR-10b and miR-29 in chronic coronary syndrome patients. The results demonstrated that microRNAs downregulating atheroprotective pathways may differ according to atherosclerotic plaque burden and progression. This finding may suggest a potential role for this miRNA (especially miR-92a) as a diagnostic marker reflecting advanced atherosclerosis with significant lesions, or even as a possible therapeutic target.