Functional Role of microRNAs in Regulating Cardiomyocyte Death

Kansakar, Urna; Varzideh, Fahimeh; Mone, Pasquale; Jankauskas, Stanislovas S.; Santulli, Gaetano

doi:10.3390/cells11060983

Cited by 29 publications

(20 citation statements)

References 151 publications

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“…We and others have shown that microRNAs (miRNAs), small non-coding RNAs of ~22 nucleotides, may serve as reliable biomarkers of various human disorders (Keller et al, 2014;Santulli et al, 2014;Sardu et al, 2014;Novak et al, 2015;Santulli, 2015;Santulli, 2016;Cammarata et al, 2018;Slota and Booth, 2019;Dama et al, 2020;Donati et al, 2021;Jankauskas et al, 2021;Kanach et al, 2021;Kansakar et al, 2022). Therefore, the microRNAs profile could be a promising biomarker candidate…”

Section: Acknowledgmentsmentioning

confidence: 99%

Mitochondrial microRNAs Are Dysregulated in Patients with Fabry Disease

Gambardella

Fiordelisi

Sorriento

et al. 2022

J Pharmacol Exp Ther

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We demonstrate for the first time that a specific signature of circulating mitochondrial microRNAs (mitomiRs) is dysregulated in Fabry disease (FD). In our study, we observed that mitomiRs regulating fundamental aspects of mitochondrial homeostasis and fitness, including expression and assembly of the respiratory chain, mitogenesis, antioxidant capacity, and apoptosis are significantly dysregulated in FD patients. Taken together, our new findings introduce mitomiRs as unprecedented biomarkers of FD and point at mitochondrial dysfunction as a novel potential mechanistic target for therapeutic approaches.

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Section: Acknowledgmentsmentioning

confidence: 99%

Mitochondrial microRNAs Are Dysregulated in Patients with Fabry Disease

Gambardella

Fiordelisi

Sorriento

et al. 2022

J Pharmacol Exp Ther

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“…The proangiogenic properties of miR-548j-5p have been demonstrated to exert a beneficial effect on hindlimb ischemia in mouse models [ 50 ]. Many miRNAs have also been identified to be involved in various types of cardiomyocyte death, making them interesting therapeutic targets in ischemic events such as acute myocardial infarction and heart failure [ 60 ].…”

Section: Discussionmentioning

confidence: 99%

miRNA Regulatory Networks Associated with Peripheral Vascular Diseases

Zalewski

Ruszel

Stępniewski

et al. 2022

JCM

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A growing body of evidence indicates a crucial role of miRNA regulatory function in a variety of mechanisms that contribute to the development of diseases. In our previous work, alterations in miRNA expression levels and targeted genes were shown in peripheral blood mononuclear cells (PBMCs) from patients with lower extremity artery disease (LEAD), abdominal aortic aneurysm (AAA), and chronic venous disease (CVD) in comparison with healthy controls. In this paper, previously obtained miRNA expression profiles were compared between the LEAD, AAA, and CVD groups to find either similarities or differences within the studied diseases. Differentially expressed miRNAs were identified using the DESeq2 method implemented in the R programming software. Pairwise comparisons (LEAD vs. AAA, LEAD vs. CVD, and AAA vs. CVD) were performed and revealed 10, 8, and 17 differentially expressed miRNA transcripts, respectively. The functional analysis of the obtained miRNAs was conducted using the miRNet 2.0 online tool and disclosed associations with inflammation and cellular differentiation, motility, and death. The miRNet 2.0 tool was also used to identify regulatory interactions between dysregulated miRNAs and target genes in patients with LEAD, AAA, and CVD. The presented research provides new information about similarities and differences in the miRNA-dependent regulatory mechanisms involved in the pathogenesis of LEAD, AAA, and CVD.

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“…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).…”

Section: Introductionmentioning

confidence: 99%

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

Mone¹,

Lombardi

Kansakar

et al. 2022

J Pharmacol Exp Ther

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Endothelial dysfunction represents a key mechanism underlying heart failure with preserved ejection fraction (HFpEF), diabetes mellitus (DM), and frailty. However, reliable biomarkers to monitor endothelial dysfunction in these patients are lacking. In this study, we evaluated the expression of a panel of circulating microRNAs (miRNAs, miRs) involved in the regulation of endothelial function in frail older adults with HFpEF and DM that were treated for 3 months with empagliflozin, metformin, or insulin. We identified a distinctive pattern of miRs that were significantly regulated in HFpEF patients compared to healthy controls and in HFpEF patients after treatment with the SGLT2 inhibitor empagliflozin. Three miRs were significantly downregulated (miR-126, miR-342-3p, and miR-638) and two were significantly upregulated (miR-21 and miR-92) in HFpEF patients compared to healthy controls. Strikingly, two of these miRs (miR-21 and miR-92) were significantly reduced in HFpEF patients after the 3-month treatment with empagliflozin whereas no significant differences in the profile of endothelial miRs were detected in patients treated with metformin or insulin. Taken together, our findings demonstrate for the first time that specific circulating miRs implied in the regulation of endothelial function are significantly regulated in frail HFpEF patients with DM and in response to empagliflozin treatment.

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Functional Role of microRNAs in Regulating Cardiomyocyte Death

Cited by 29 publications

References 151 publications

Mitochondrial microRNAs Are Dysregulated in Patients with Fabry Disease

Mitochondrial microRNAs Are Dysregulated in Patients with Fabry Disease

miRNA Regulatory Networks Associated with Peripheral Vascular Diseases

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

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