Higher Expression of miR-155 and miR-103 in Patients with Gitelman Syndrome: Potential Implications for Angiotensin II-Induced Cardiovascular Remodeling in Hypertension

INTRODUCTION: miR-155 and miR-103 are multifunctional miRNAs known to be involved in angiotensin II (Ang II) signaling linked with hypertension and cardiovascular remodeling, although their role is controversial and not completely clarified. Gitelman syndrome (GS), rare genetic tubulopathy, represents a human model of an endogenous Ang II signaling antagonism and GS patients are in fact protected from Ang II-mediated cardiovascular remodeling. This study aimed to compare the expression of miR-155 and miR-103 in patients with GS vs. healthy controls. METHODS: Sixteen patients with GS and 21 age- and sex-matched healthy controls were recruited from an active cohort at the Nephrology Unit of Padua University Hospital and among volunteers, respectively. The specific miRNA population was isolated from plasma, and miR-155 and miR-103 were then quantified using droplet PCR and TaqMan miRNA assays and compared using the Mann-Whitney U test. RESULTS: In GS patients, expression of miR-155 (528.7 vs. 64.40 copies/sample, p = 0.0015) and miR-103 (80.25 vs. 23.94 copies/sample, p = 0.0034) were significantly higher compared to the control group. CONCLUSION: This is the first study investigating circulating miRNAs in GS patients. The difference in expression levels of miR-155 and miR-103 in these patients compared to healthy subjects suggests that these miRNAs may be associated with mechanisms contributing to their well-established protection from Ang II-mediated cardiovascular remodeling.