Long noncoding RNAs in cardiometabolic disorders

Juni, Rio P.; Hart, Kelly C. ’t; Houtkooper, Riekelt H.; Boon, Reinier A.

doi:10.1002/1873-3468.14370

Cited by 11 publications

(16 citation statements)

References 162 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The human genome encodes about 100,000 lncRNAs, but a function has only been identified for <5% of them. The underlying reason is their minor conservation between species and their functional heterogeneity (Juni et al., 2022 ). This functional versatility of lncRNAs is reflected by the different levels at which they can modulate gene expression: as lncRNAs can interact with DNA, RNA and chromatin, they can regulate gene transcription on a transcriptional, post‐transcriptional or epigenetic level (Cui et al., 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Higher gestational weight gain delays wound healing and reduces expression of long non‐coding RNA KLRK1‐AS1 in neonatal endothelial progenitor cells

Weiss,

Schrüfer,

Tocantins

et al. 2023

The Journal of Physiology

Self Cite

View full text Add to dashboard Cite

High gestational weight gain (GWG) is a cardiovascular risk factor and may disturb neonatal endothelial function. Long non‐coding RNAs (lncRNAs) regulate gene expression epigenetically and can modulate endothelial function. Endothelial colony forming cells (ECFCs), circulating endothelial precursors, are a recruitable source of endothelial cells and sustain endothelial function, vascular growth and repair. We here investigated whether higher GWG affects neonatal ECFC function and elucidated the role of lncRNAs herein. Wound healing of umbilical cord blood‐derived ECFCs after pregnancies with GWG <13 kg versus >13 kg was determined in a scratch assay and based on monolayer impedance after electric wounding (electric cell‐substrate impedance sensing, ECIS). LncRNA expression was analysed by RNA sequencing. The function of killer cell lectin‐like receptor K1 antisense RNA (KLRK1‐AS1) was investigated after siRNA‐based knockdown. Closure of the scratch was delayed by 25% (P = 0.041) in the higher GWG group and correlated inversely with GWG (R = −0.538, P = 0.012) in all subjects (n = 22). Similarly, recovery of the monolayer barrier after electric wounding was delayed (−11% after 20 h; P = 0.014; n = 15). Several lncRNAs correlated with maternal GWG, the most significant one being KLRK1‐AS1 (log2 fold change = −0.135, P < 0.001, n = 35). KLRK1‐AS1 knockdown (n = 4) reduced barrier recovery after electric wounding by 21% (P = 0.029) and KLRK1‐AS1 expression correlated with the time required for wound healing for both scratch (R = 0.447, P = 0.033) and impedance‐based assay (R = 0.629, P = 0.014). Higher GWG reduces wound healing of neonatal ECFCs, and lower levels of the lncRNA KLRK1‐AS1 may underlie this. imageKey points Maternal cardiovascular risk factors such as diabetes, obesity and smoking in pregnancy disturb fetal endothelial function, and we here investigated whether also high gestational weight gain (GWG) has an impact on fetal endothelial cells. Circulating endothelial progenitor cells (endothelial colony forming cells, ECFCs) are highly abundant in the neonatal blood stream and serve as a circulating pool for vascular growth and repair. We revealed that higher GWG delays wound healing capacity of ECFCs in vitro. We identified the regulatory RNA lncRNA KLRK1‐AS1 as a link between GWG and delayed ECFC wound healing. Our data show that high GWG, independent of pre‐pregnancy BMI, affects neonatal ECFC function.

show abstract

Section: Discussionmentioning

confidence: 99%

Higher gestational weight gain delays wound healing and reduces expression of long non‐coding RNA KLRK1‐AS1 in neonatal endothelial progenitor cells

Weiss,

Schrüfer,

Tocantins

et al. 2023

The Journal of Physiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Furthermore, lncRNAs have been identified in syntenic genomic regions across species, known as locus-conserved lncRNAs, which typically serve conserved functions ( 150 ). Although lncRNAs are usually less abundant than mRNAs, they tend to display stronger tissue-specific expression patterns ( 152 ).…”

Section: Non-coding Rnas In Pathophysiological Processes Leading To H...mentioning

confidence: 99%

“…The sub-cellular localization of lncRNAs plays a crucial role in determining their functions ( 152 ). The majority of lncRNAs are found within the nucleus, where they associate with chromatin, while some fractions localize to the cytoplasm ( 147 ).…”

Section: Non-coding Rnas In Pathophysiological Processes Leading To H...mentioning

confidence: 99%

Non-coding RNAs in the pathophysiology of heart failure with preserved ejection fraction

Jalink,

Schonk,

Boon

et al. 2024

Front. Cardiovasc. Med.

Self Cite

View full text Add to dashboard Cite

Heart failure with preserved ejection fraction (HFpEF) is the largest unmet clinical need in cardiovascular medicine. Despite decades of research, the treatment option for HFpEF is still limited, indicating our ongoing incomplete understanding on the underlying molecular mechanisms. Non-coding RNAs, comprising of microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), are non-protein coding RNA transcripts, which are implicated in various cardiovascular diseases. However, their role in the pathogenesis of HFpEF is unknown. Here, we discuss the role of miRNAs, lncRNAs and circRNAs that are involved in the pathophysiology of HFpEF, namely microvascular dysfunction, inflammation, diastolic dysfunction and cardiac fibrosis. We interrogated clinical evidence and dissected the molecular mechanisms of the ncRNAs by looking at the relevant in vivo and in vitro models that mimic the co-morbidities in patients with HFpEF. Finally, we discuss the potential of ncRNAs as biomarkers and potential novel therapeutic targets for future HFpEF treatment.

show abstract

“…This archetype defines a set of lncRNAs that are present at a particular genomic location in a space and time-specific manner to signal for transcriptional activation or repression (e.g KCNQ1OT1) [ 25 , 29 ] as well as lncRNAs that by itself do not have regulatory function, but its transcription process does (e.g. upperhand) [ 31 , 32 ]. By definition, signal lncRNAs serve as mere indicators of transcriptional activity without a secondary biological function as transcript [ 29 ].…”

Section: Long Non-coding Rnasmentioning

confidence: 99%

The multifaceted actions of the lncRNA H19 in cardiovascular biology and diseases

2022

Self Cite

View full text Add to dashboard Cite

Cardiovascular diseases are the leading cause of death and debility worldwide. Various molecular mechanisms have been studied to better understand the development and progression of cardiovascular pathologies with hope to eradicate these diseases. With the advancement of the sequencing technology, it is revealed that the majority of our genome is non-coding. A growing body of literature demonstrates the critical role of long non-coding RNAs (lncRNAs) as epigenetic regulators of gene expression. LncRNAs can regulate cellular biological processes through various distinct molecular mechanisms. The abundance of lncRNAs in the cardiovascular system indicates their significance in cardiovascular physiology and pathology. LncRNA H19, in particular, is a highly evolutionarily conserved lncRNA that is enriched in cardiac and vascular tissue, underlining its importance in maintaining homeostasis of the cardiovascular system. In this review, we discuss the versatile function of H19 in various types of cardiovascular diseases. We highlight the current literature on H19 in the cardiovascular system and demonstrate how dysregulation of H19 induces the development of cardiovascular pathophysiology.

show abstract

Long noncoding RNAs in cardiometabolic disorders

Cited by 11 publications

References 162 publications

Higher gestational weight gain delays wound healing and reduces expression of long non‐coding RNA KLRK1‐AS1 in neonatal endothelial progenitor cells

Higher gestational weight gain delays wound healing and reduces expression of long non‐coding RNA KLRK1‐AS1 in neonatal endothelial progenitor cells

Non-coding RNAs in the pathophysiology of heart failure with preserved ejection fraction

The multifaceted actions of the lncRNA H19 in cardiovascular biology and diseases

Contact Info

Product

Resources

About