Malat1 deficiency prevents neonatal heart regeneration by inducing cardiomyocyte binucleation

Aslan, Galip Servet; Manavski, Yosif; Fouani, Youssef; Shumliakivska, Mariana; Kettenhausen, Lisa; Kirchhof, Luisa; Guenther, Stefan; Fischer, Ariane; Luxán, Guillermo; Dimmeler, Stefanie

doi:10.1172/jci.insight.162124

Cited by 5 publications

(2 citation statements)

References 66 publications

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“…Sections for immunohistochemistry were prepared as described before 33 including the antigen retrieval step. Capillary density was visualized using the following primary and secondary antibodies: Isolectin B4 (Vector) and Streptavidin Alexa488 (Invitrogen), wheat germ agglutinin Alexa647 (Thermo Fisher), anti-actin alpha smooth muscle Cy3 (Sigma) and Hoechst 33342 (Anaspec).…”

Section: Immunohistochemistrymentioning

confidence: 99%

The aging-induced long non-coding RNAMIRIALcontrols endothelial cell and mitochondrial function

Kohnle,

Koziarek,

Warwick

et al. 2024

Preprint

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BackgroundVascular aging is characterized by the progressive deterioration of endothelial function. Long non-coding RNAs (lncRNAs) are critical regulators of gene expression and protein function. However, their involvement in aging-related dysregulation of endothelial cell function remains largely unknown. Here, we aim to characterize the aging-regulated lncRNAMIRIALin endothelial cells.Methods + ResultsWe initially identifiedMirialas an aging-induced lncRNA in RNA sequencing data of mouse cardiac endothelial cells. In human umbilical vein endothelial cells (HUVECs), gapmer-mediated knockdown ofMIRIALled to decreases in proliferation, migration and basal angiogenic sprouting. Additionally,MIRIALknockdown led to increased mitochondrial mass, spare respiratory capacity, and vascular endothelial growth factor (VEGF)-stimulated sprouting. Mechanistically, we demonstrate thatMIRIALforms anRNA·DNA:DNA triple helix (triplex) with a regulatory region of the quiescence-promoting Forkhead Box O1 (FOXO1) gene, thus inducing its expression. The formation of this triplex involves anAluelement within theMIRIALtranscript, representing a previously undescribed mechanism of action for a lncRNA. Further, we generated a globalMirialknockout mouse line of. Angiogenic sprouting of aortic rings fromMirialknockout mice was reduced under basal conditions, but increased after VEGF administration, validating thein vitroangiogenic phenotype. Importantly, cardiac contractile function after acute myocardial infarction is severely reduced inMirialknockout mice, as compared to wild-type littermates.ConclusionsThe lncRNAMIRIALis an aging-induced regulator of endothelial quiescence and metabolism.Abstract Figure

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Section: Immunohistochemistrymentioning

confidence: 99%

The aging-induced long non-coding RNAMIRIALcontrols endothelial cell and mitochondrial function

Kohnle,

Koziarek,

Warwick

et al. 2024

Preprint

Self Cite

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“…LncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been found to be associated with the modulation of myocardial ischemic injury, atherosclerotic progression, cellular senescence, and systemic inflammation [ 100 , 101 , 102 ]. It shows promise as a potential biomarker for acute myocardial infarction [ 103 ].…”

Section: The Role Of Msc-derived Lncrnas In Cardiac Injury and Repairmentioning

confidence: 99%

Mesenchymal Stem Cell-Derived Long Noncoding RNAs in Cardiac Injury and Repair

Tran,

Cruz,

Chan

et al. 2023

Cells

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Cardiac injury, such as myocardial infarction and heart failure, remains a significant global health burden. The limited regenerative capacity of the adult heart poses a challenge for restoring its function after injury. Mesenchymal stem cells (MSCs) have emerged as promising candidates for cardiac regeneration due to their ability to differentiate into various cell types and secrete bioactive molecules. In recent years, attention has been given to noncoding RNAs derived from MSCs, particularly long noncoding RNAs (lncRNAs), and their potential role in cardiac injury and repair. LncRNAs are RNA molecules that do not encode proteins but play critical roles in gene regulation and cellular responses including cardiac repair and regeneration. This review focused on MSC-derived lncRNAs and their implications in cardiac regeneration, including their effects on cardiac function, myocardial remodeling, cardiomyocyte injury, and angiogenesis. Understanding the molecular mechanisms of MSC-derived lncRNAs in cardiac injury and repair may contribute to the development of novel therapeutic strategies for treating cardiovascular diseases. However, further research is needed to fully elucidate the potential of MSC-derived lncRNAs and address the challenges in this field.

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RNA binding proteins in cardiovascular development and disease

Verma,

Kuyumcu-Martinez

2024

Current Topics in Developmental Biology

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Malat1 deficiency prevents neonatal heart regeneration by inducing cardiomyocyte binucleation

Cited by 5 publications

References 66 publications

The aging-induced long non-coding RNAMIRIALcontrols endothelial cell and mitochondrial function

The aging-induced long non-coding RNAMIRIALcontrols endothelial cell and mitochondrial function

Mesenchymal Stem Cell-Derived Long Noncoding RNAs in Cardiac Injury and Repair

RNA binding proteins in cardiovascular development and disease

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