LncRNA CARMN inhibits abdominal aortic aneurysm formation and vascular smooth muscle cell phenotypic transformation by interacting with SRF DOI Creative Commons

Shenrong Liu,

Haobin Zhou,

Dunzheng Han

et al.

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)

Published: April 10, 2024

Abstract Phenotypic transformation of vascular smooth muscle cells (VSMCs) plays a crucial role in abdominal aortic aneurysm (AAA) formation. CARMN, highly conserved, VSMC-enriched long noncoding RNA (lncRNA), is integral orchestrating various pathologies by modulating the phenotypic dynamics VSMCs. The influence CARMN on AAA formation, particularly its mechanisms, remains enigmatic. Our research, employing single-cell and bulk sequencing, has uncovered significant suppression specimens, which correlates strongly with contractile function This reduced expression was consistent both 7- 14-day porcine pancreatic elastase (PPE)-induced mouse models human clinical cases. Functional analyses disclosed that diminution exacerbated PPE-precipitated whereas augmentation conferred protection against such Mechanistically, we found CARMN's capacity to bind SRF, thereby amplifying driving transcription VSMC marker genes. In addition, our findings indicate an enhancement CAMRN transcription, facilitated binding NRF2 promoter region. study indicated protective preventing formation restrains through interaction SRF. Additionally, observed augmented These suggest potential as viable therapeutic target treatment AAA. Graphical abstract

Language: Английский

LncRNA VINAS regulates atherosclerosis by modulating NF-κB and MAPK signaling DOI Creative Commons
Viorel Simion,

Haoyang Zhou,

Jacob B. Pierce

et al.

JCI Insight, Journal Year: 2020, Volume and Issue: 5(21)

Published: Oct. 6, 2020

Long noncoding RNAs (lncRNAs) play important roles in regulating diverse cellular processes the vessel wall, including atherosclerosis. RNA-Seq profiling of intimal lesions revealed a lncRNA, VINAS (Vascular INflammation and Atherosclerosis lncRNA Sequence), that is enriched aortic intima regulates vascular inflammation. Aortic expression fell with atherosclerotic progression rose regression. knockdown reduced lesion formation by 55% LDL receptor-deficient (LDLR-/-) mice, independent effects on circulating lipids, decreasing inflammation wall. Loss- gain-of-function studies vitro demonstrated serves as critical regulator modulating NF-κB MAPK signaling pathways. decreased key inflammatory markers, such MCP-1, TNF-α, IL-1β, COX-2, endothelial cells (ECs), smooth muscle cells, bone marrow-derived macrophages. Moreover, silencing leukocyte adhesion molecules VCAM-1, E-selectin, ICAM-1 monocyte to ECs. DEP domain containing 4 (DEPDC4), an evolutionary conserved human ortholog approximately 74% homology, showed similar regulation pig specimens. DEPDC4 replicated antiinflammatory These findings reveal potentially novel inflammation, broad implications for diseases.

Language: Английский

Citations

67
Long Noncoding RNAs in Atherosclerosis and Vascular Injury DOI Creative Commons
Jacob B. Pierce, Mark W. Feinberg

Arteriosclerosis Thrombosis and Vascular Biology, Journal Year: 2020, Volume and Issue: 40(9), P. 2002 - 2017

Published: July 23, 2020

Despite major advances in the primary and secondary prevention of atherosclerosis its risk factors, atherosclerotic cardiovascular disease remains a clinical financial burden on individuals health systems worldwide. In addition, neointima formation proliferation due to mechanical trauma vessel wall during percutaneous coronary interventions can lead vascular restenosis limit longevity effectiveness revascularization. Long noncoding RNAs (lncRNAs) have emerged as novel class epigenetic regulators with critical roles pathogenesis following injury. Here, we provide an in-depth review lncRNAs that regulate development or contribute We describe diverse array intracellular mechanisms by which exert their regulatory effects. highlight utility challenges biomarkers. Finally, discuss immense translational potential strategies for targeting them therapeutically using oligonucleotide-based therapeutics gene therapy platforms.

Language: Английский

Citations

53
Epi-Drugs in Heart Failure DOI Creative Commons
Era Gorica, S A Mohammed, Samuele Ambrosini

et al.

Frontiers in Cardiovascular Medicine, Journal Year: 2022, Volume and Issue: 9

Published: July 13, 2022

Unveiling the secrets of genome’s flexibility does not only foster new research in field, but also gives rise to exploration and development novel epigenetic-based therapies as an approach alleviate disease phenotypes. A better understanding chromatin biology (DNA/histone complexes) non-coding RNAs (ncRNAs) has enabled epigenetic drugs able modulate transcriptional programs implicated cardiovascular diseases. This particularly applies heart failure, where networks have shown underpin several pathological features, such left ventricular hypertrophy, fibrosis, cardiomyocyte apoptosis microvascular dysfunction. Targeting signals might represent a promising approach, especially patients with failure preserved ejection fraction (HFpEF), prognosis remains poor breakthrough yet be approved. In this setting, epigenetics can employed for customized therapeutic approaches thus paving way personalized medicine. Even though beneficial effects epi-drugs are gaining attention, number compounds used clinical practice low suggesting that more selective needed. From DNA-methylation changes RNAs, we establish brand-new regulations drug targets aim restoring healthy epigenomes failing heart. present review, bring timeline epi-drug discovery development, highlighting emerging role failure.

Language: Английский

Citations

35
The role of long noncoding RNAs in ocular angiogenesis and vascular oculopathy DOI Creative Commons

Pranali Gandhi,

Yuzhi Wang,

Guigang Li

et al.

Cell & Bioscience, Journal Year: 2024, Volume and Issue: 14(1)

Published: March 23, 2024

Long noncoding RNAs (lncRNAs) are RNA transcripts over 200 nucleotides in length that do not code for proteins. Initially considered a genomic mystery, an increasing number of lncRNAs have been shown to vital roles physiological and pathological conditions by regulating gene expression through diverse mechanisms depending on their subcellular localization. Dysregulated angiogenesis is responsible various vascular oculopathies, including diabetic retinopathy, retinopathy prematurity, age-related macular degeneration, corneal neovascularization. While anti-VEGF treatment available, it curative, long-term outcomes suboptimal, some patients unresponsive. To better understand these diseases, researchers investigated the role models oculopathies. This review summarizes recent research ocular angiogenesis, pro-angiogenic ANRIL, HOTAIR, HOTTIP, H19, IPW, MALAT1, MIAT, NEAT1, TUG1, anti-angiogenic MEG3 PKNY, human/primate specific lncEGFL7OS, discussing functions action

Language: Английский

Citations

7
LncRNA CARMN inhibits abdominal aortic aneurysm formation and vascular smooth muscle cell phenotypic transformation by interacting with SRF DOI Creative Commons

Shenrong Liu,

Haobin Zhou,

Dunzheng Han

et al.

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)

Published: April 10, 2024

Abstract Phenotypic transformation of vascular smooth muscle cells (VSMCs) plays a crucial role in abdominal aortic aneurysm (AAA) formation. CARMN, highly conserved, VSMC-enriched long noncoding RNA (lncRNA), is integral orchestrating various pathologies by modulating the phenotypic dynamics VSMCs. The influence CARMN on AAA formation, particularly its mechanisms, remains enigmatic. Our research, employing single-cell and bulk sequencing, has uncovered significant suppression specimens, which correlates strongly with contractile function This reduced expression was consistent both 7- 14-day porcine pancreatic elastase (PPE)-induced mouse models human clinical cases. Functional analyses disclosed that diminution exacerbated PPE-precipitated whereas augmentation conferred protection against such Mechanistically, we found CARMN's capacity to bind SRF, thereby amplifying driving transcription VSMC marker genes. In addition, our findings indicate an enhancement CAMRN transcription, facilitated binding NRF2 promoter region. study indicated protective preventing formation restrains through interaction SRF. Additionally, observed augmented These suggest potential as viable therapeutic target treatment AAA. Graphical abstract

Language: Английский

Citations

7