Abstract Introduction Idiopathic pulmonary arterial hypertension (IPAH) and Eisenmenger syndrome (ES) are distinct forms of pulmonary hypertension marked by progressive vascular remodeling and increased pulmonary vascular resistance. IPAH results from primary vascular dysfunction, whereas ES arises secondary to congenital heart defects with systemic-to-pulmonary shunting. MicroRNAs (miRNAs) regulate angiogenesis, inflammation, and smooth muscle proliferation, offering promise as biomarkers to differentiate these conditions. Objectives To compare miRNA expression profiles in IPAH and ES patients and correlate them with clinical parameters to elucidate vascular remodeling mechanisms and identify potential diagnostic and therapeutic targets. Methods The study enrolled 12 IPAH and 19 ES patients. Clinical data (age, gender, NT-proBNP, and 6-minute walk test 6MWT distances) were collected. Peripheral blood was obtained, total RNA extracted, and miRNA profiling performed using the TaqMan® Array Human MicroRNA A+B Cards Set (754 miRNAs). Differential expression was analyzed via the ΔΔCt method (normalized to endogenous controls), with Relative Quantification (RQ) calculated as RQ=2^ (−ΔΔCt) (where RQ 1 indicates upregulation; RQ 1, downregulation). Results Eighteen miRNAs were significantly differentially expressed (fold change 2, p 0. 05). In IPAH, there was marked upregulation of pro-proliferative/anti-apoptotic miRNAs (e. g. , miR-30a-5p, RQ: 19. 1; miR-501, RQ: 21. 2; miR-875-5p, RQ: 223. 5), while ES patients showed higher expression of miRNAs with anti-inflammatory/endothelial-protective roles (e. g. , miR-30e-3p, RQ: 0. 44; miR-629, RQ: 0. 31; miR-603, RQ: 0. 34), with miR-520c-3p markedly downregulated in IPAH (RQ: 0. 015). Additionally, miR-378, miR-151-3p, and miR-720 were lower in IPAH. Clinically, the IPAH group (mean age 47 ± 12 years, 67% female) had significantly higher NT-proBNP median 1800 pg/mL (IQR: 1200–2400) and reduced 6MWT distances median 320 m (IQR: 280–360) compared to ES (mean age 35 ± 10 years, 58% female; NT-proBNP: median 900 pg/mL IQR: 700–1100; 6MWT: median 420 m IQR: 380–460) (p 0. 01 for NT-proBNP and 6MWT; p=0. 01 for age; gender NS). Pathway analysis implicated key networks—including TGF-β, HIF-1α, and NF-κB—in mediating these miRNA alterations. Conclusion Distinct miRNA profiles in IPAH and ES correlate with differing clinical characteristics, suggesting divergent molecular mechanisms of vascular remodeling. The upregulation of proliferative miRNAs in IPAH, combined with higher NT-proBNP and lower exercise capacity, contrasts with a more protective miRNA signature in ES—highlighting the potential of miRNA profiling as a diagnostic and therapeutic tool in pulmonary hypertension. Further studies with larger cohorts are warranted.
Miśkowiec et al. (Sat,) studied this question.