Exosomal miR-145 and miR-885 Regulate Thrombosis in COVID-19

Abstract

We hypothesized that exosomal microRNAs (miRNAs) could be implied in the pathogenesis of thromboembolic complications in COVID-19. We isolated circulating exosomes from COVID-19 patients and then we divided our population in two arms based on the D-dimer level on hospital admission. We observed that exosomal miR-145 and miR-885 significantly correlate with D-Dimer levels. Moreover, we demonstrate that human endothelial cells express the main cofactors needed for SARS-CoV-2 internalization, including ACE2, TMPRSS2, and CD-147. Interestingly, human endothelial cells treated with serum from COVID-19 patients release significantly less miR-145 and miR-885, exhibit increased apoptosis, and display significantly impaired angiogenetic properties compared to cells treated with non-COVID-19 serum. Taken together, our data indicate that exosomal miR-145 and miR-885 are essential in modulating thromboembolic events in COVID-19.

Combining L-Arginine with vitamin C improves long-COVID symptoms: The LINCOLN Survey

“…targeting endothelial dysfunction in Long-COVID. Indeed, endothelial cell infection with consecutive inflammatory cell recruitment and endothelial dysfunction could explain the impaired microcirculation observed across vascular beds in COVID-19, triggering vasoconstriction, ischemia, and a pro-coagulant state 92 , 93 , 94 , 95 . Consistent with our view, several investigators had proposed that endotheliitis could be a critical mechanism underlying systemic impaired microcirculatory function observed in different vascular beds in patients experiencing Long-COVID symtoms 92 , 96 .…”

Exosomal Micro-RNAs as Intercellular Communicators in Idiopathic Pulmonary Fibrosis

“…Although this review was focused on the analysis of exosomal-miRNAs in IPF, the most recent data about exosomal-miRNAs in malignant pathologies [ 176 ], diabetes mellitus [ 177 ], other lung diseases [ 178 ], and emergent diseases such as COVID-19 [ 179 ], clearly highlight the importance of further advancing this line of research.…”

Empagliflozin Improves the MicroRNA Signature of Endothelial Dysfunction in Patients with Heart Failure with Preserved Ejection Fraction and Diabetes

“…A physical frailty assessment was performed following the Fried Criteria, as we previously described (Mone et al, 2022b;Mone et al, 2022d). A diagnosis of frailty status was made with at least three out of the following five points: 1) Weight loss (unintentional loss of ≥4.5 kg in the past year), 2) weakness (handgrip strength in the lowest 20% quintile at baseline, adjusted for sex and body mass index, 3) exhaustion (poor endurance and energy), 4) slowness (walking speed under the lowest quintile adjusted for sex and height), 5) Low physical activity level (lowest quintile of kilocalories of physical activity during the past week).…”

“…MicroRNAs (miRs) are small non-coding RNAs molecules of 18-24 nucleotides, which typically repress messenger RNAs (mRNAs) by binding their 3′ untranslated region (Santulli, 2015;Fridrichova and Zmetakova, 2019;Stavast and Erkeland, 2019;Hu et al, 2021;Mirzaei et al, 2021;Mone et al, 2021b;Bielska et al, 2022;Karagiannopoulos et al, 2022;Mauro et al, 2022;Moisoiu et al, 2022;Qiu et al, 2022;Traber and Yu, 2022;Yaylim et al, 2022;Zeng et al, 2022). Substantial evidence has shown that miRs exert their activity in many biological processes and several miRs have been proposed as biomarkers and potential targets of novel therapeutic strategies (Creemers et al, 2012;Wronska et al, 2015;Barwari et al, 2016;Zarone et al, 2017;Chen et al, 2018;Wong et al, 2018;Morelli et al, 2019;Kawasaki et al, 2020;Wang et al, 2020;Fonseca et al, 2021;Gambardella et al, 2021;Bonnet et al, 2022;Gambardella et al, 2022a;Gambardella et al, 2022b;Kansakar et al, 2022;Varzideh et al, 2022). Several investigators have linked miRs to frailty for their involvement in inflammation, endothelial dysfunction, and senescence (Quinn and O'Neill, 2011;Olivieri et al, 2012;Geiger and Dalgaard, 2017;Rusanova et al, 2019;Bu et al, 2021).…”