Patients with aldosterone-producing adenoma had 19 significantly differentially expressed miRNAs in circulating EVs compared to those with essential hypertension, linking to pro-inflammatory pathways.
Observational (n=24)
Does the small RNA cargo of circulating extracellular vesicles differ between patients with aldosterone-producing adenoma and essential hypertension?
Circulating extracellular vesicles in patients with aldosterone-producing adenomas carry a distinct pro-inflammatory and anti-fibrotic miRNA cargo compared to essential hypertension, potentially contributing to increased cardiovascular risk.
Objective: Patients with primary aldosteronism (PA) display marked vascular target-organ damage, characterized by endothelial dysfunction, inflammation, fibrosis, and the development of atherosclerosis. Extracellular vesicles (EVs) play a pivotal role in intercellular communication by transferring a wide range of cargos, including small non-coding RNAs. Design and method: This study aimed to characterize the small RNA cargo of circulating EVs from patients with aldosterone-producing adenoma (APA) and patients with essential hypertension (EH), in order to determine whether disease-specific alterations in these biomarkers are associated with distinct biological processes and molecular targets. EVs were isolated by ultracentrifugation from serum samples obtained from 12 APA patients and 12 EH patients, matched for cardiovascular risk profile. Small RNA sequencing was performed to compare the miRNA cargo between APA and EH patients, as well as in APA patients before and after adrenalectomy. Bioinformatic analyses, including network-cluster analysis, were conducted to identify pathways enriched in each condition, and selected miRNA–mRNA target pairs were further evaluated through in vitro validation in human microvascular endothelial cells (HMECs). Results: Small RNA profiling identified 19 miRNAs that were significantly differentially expressed in APA patients, with 6 upregulated and 13 downregulated. Bioinformatic analyses, including network-cluster analysis, revealed associations with pro-inflammatory pathways related to MAPK signaling in APA patients and with TGFβ-related pathways in EH patients. In vitro inhibition of miR-769-5p (downregulated in APA patients) in HMECs resulted in increased MAPK1 expression, whereas mimicking of miR-486-5p (upregulated in APA patients) led to reduced SMAD2 expression, whose intracellular accumulation is known to increase TGFβ signaling. Following laparoscopic adrenalectomy, circulating EV levels of miR-486-5p were significantly reduced in APA patients. Treatment of HMEC with aldosterone showed increased expression of miR-486-5p, which was reverted by eplerenone treatment. Conclusions: Analysis of the small RNA cargo of circulating EVs from APA patients revealed associations with pro-inflammatory and anti-fibrotic pathways, with potential increase of inflammation and destabilization of the atherosclerotic plaque, contributing to the increase of cardiovascular events observed in patients with APA.
Buffolo et al. (Fri,) conducted a observational in Aldosterone-producing adenoma and essential hypertension (n=24). Aldosterone-producing adenoma vs. Essential hypertension was evaluated on Differential expression of small RNA cargo (miRNAs) in circulating extracellular vesicles. Patients with aldosterone-producing adenoma had 19 significantly differentially expressed miRNAs in circulating EVs compared to those with essential hypertension, linking to pro-inflammatory pathways.