Plasma exosomes and circulating exosomal miR-21 and miR-133a are associated with reverse remodeling in patients with severe primary mitral regurgitation undergoing to surgical repair

Background: Mitral regurgitation (MR) is associated to adverse remodeling of left ventricle (LV) and to progressive reduction of LV ejection fraction (LVEF). Although surgery is the mainstay of treatment, the most appropriate timing remains debated. Exosomes are circulating vectors of inter-cell signaling mediated by several molecules stored within the envelope including micro-RNA (mRNAs). MiRNAs are small noncoding ribonucleic acid molecules with regulatory roles involved in many biological process including cardiovascular diseases. Methods and results: We aimed to investigate if circulating exosomal concentration and specific exosomal miRNAs (miR-1; miR-133a; miR-21; miR-208a) isolated from plasma are biomarkers of cardiac remodeling and reduced contractile reserve in patients with severe MR. Nineteen severe primary MR patients underwent to cardiac magnetic resonance imaging and to exosomes isolation and miRNAs analysis before (T0) and after 6 months from surgery (T1). Eight healthy controls were enrolled to comparison. According to LV reverse remodeling, patients were clustered in the “LV reverse remodeling group” (LV-Rev-Rem) or in the “No LV reverse remodeling group” (No-LV-Rev-Rem), patients were also divided in the “reduction-LVEF” and “preserved-LVEF” groups according to LVEF drop. LV-Rev-Rem group and LVEF-preserved group had higher concentration of exosomes at T1 in comparison to the respective groups and controls. Mir-21 [1.575 (0.6200 – 6.745) vs 0.3350 (0.1800 – 1.470), P=0.02] and miR 133a [1.420 (1.060 – 2.465) vs 0,440 (0.285 – 1.310), P=0.05] are upregulated at T1 in LV-Rev-Rem in comparison to No-LV-reverse-rem group. Conclusions: Circulating exosomes and miRNAs may represent innovative biomarkers of contractile dysfunction and LV remodeling in patients with severe MR.