Age-Disturbed Vascular Extracellular Matrix Links to Abdominal Aortic Aneurysms DOI

Zhenping Yu,

Andong Wu,

Ke Hao

et al.

The Journals of Gerontology Series A, Journal Year: 2024, Volume and Issue: 79(11)

Published: Aug. 12, 2024

Abdominal aortic aneurysm (AAA) is a common but life-threatening vascular condition in men at an advanced age. However, the underlying mechanisms of age-increased incidence and mortality AAA remain elusive. Here, we performed RNA sequencing (RNA-seq) mouse aortas from males (young: 3-month, n = 4 vs old: 23-month, 4) integrated with data sets human 20-39, 47 60-79 years, 92) GTEx project set (GSE183464) for to search age-shifted genes, their relevant biological processes, signaling pathways. Angiotensin II-induced mice was used verify critical findings. We found 1 001 genes transcriptionally changed ages both human. Most were enriched intracellularly processes included mitochondrial function translational controls, whereas age-decreased largely localized extracellular regions cell periphery involved associated matrix (ECM). Fifty-one known dominantly region. The had shared functional influences on ECM organization, apoptosis, angiogenesis. Aorta angiotensin exhibited similar phenotypic changes that old mice. Together, present conserved transcriptional signature aging provide evidence dysfunction imbalanced ribosomal homeostasis act likely as driven-forces age-disturbed substrate developing AAA.

Language: Английский

The Role of the MAPK Signaling Pathway in Cardiovascular Disease: Pathophysiological Mechanisms and Clinical Therapy DOI Open Access
Xueyang Wang, Ruiqi Liu, Dan Liu

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2667 - 2667

Published: March 16, 2025

Cardiovascular disease (CVD) is a serious global health issue with high mortality rates worldwide. Despite the numerous advancements in study of CVD pathogenesis recent years, further summarization and elaboration specific molecular pathways are required. An extensive body research has been conducted to elucidate association between MAPK signaling pathway, which present all eukaryotic organisms, cardiovascular disease. This review aims provide comprehensive summary on over past five years. The primary focus four diseases: heart failure, atherosclerosis, myocardial ischemia–reperfusion injury, cardiac hypertrophy. will also address pathophysiological mechanisms diseases, objective proposing novel clinical treatment strategies for CVD.

Language: Английский

Citations

1
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
Heritable thoracic aortic disease: a literature review on genetic aortopathies and current surgical management DOI
Alexander Mills, Harleen K. Sandhu, Yuki Ikeno

et al.

General Thoracic and Cardiovascular Surgery, Journal Year: 2024, Volume and Issue: 72(5), P. 293 - 304

Published: March 14, 2024

Language: Английский

Citations

6
KLF15 maintains contractile phenotype of vascular smooth muscle cells and prevents thoracic aortic dissection by interacting with MRTFB DOI Creative Commons

Guangming Fang,

Yexuan Tian,

Shan Huang

et al.

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: 300(5), P. 107260 - 107260

Published: April 4, 2024

Thoracic aortic dissection (TAD) is a highly dangerous cardiovascular disorder caused by weakening of the wall, resulting in sudden tear internal face. Progressive loss contractile apparatus vascular smooth muscle cells (VSMCs) major event TAD. Exploring endogenous regulators essential for phenotype VSMCs may aid development strategies to prevent Krüppel-like factor 15 (KLF15) overexpression was reported inhibit TAD formation; however, mechanisms which KLF15 prevents formation and whether regulates are not well understood. Therefore, we investigated these unknown aspects function. We found that expression reduced human samples β-aminopropionitrile monofumarate-induced mouse model. Klf15KO mice susceptible both monofumarate- angiotensin II-induced deficiency results VSMC contractility exacerbated inflammation extracellular matrix degradation. Mechanistically, interacts with myocardin-related transcription B (MRTFB), potent serum response coactivator drives gene expression. silencing represses MRTFB-induced activation genes VSMCs. Thus, cooperates MRTFB promote VSMCs, its dysfunction exacerbate These findings indicate be novel therapeutic target treatment

Language: Английский

Citations

4
Ponatinib alleviates non-alcoholic steatohepatitis through TFEB-mediated autophagy DOI Creative Commons

Zhuomiao Lin,

Meiqing Yang,

Xin Yu

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 7, 2025

Non-alcoholic steatohepatitis (NASH) is a progressive liver disease with lipid accumulation, inflammation, and fibrosis. Ponatinib, third-generation tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia, was found to improve metabolic disorders in mice. However, role ponatinib inflammation fibrosis remains be elucidated. Here we aimed determine effect non-alcoholic steatohepatitis. We explored function mechanism using mouse model NASH induced by methionine choline deficient (MCD) diet LO2 cells cultured MCD mimic medium. Here, that reduced deposition, fibrosis, without affecting body weight blood glucose. Meanwhile, attenuated further discovered expression levels LC3II lysosomal associated membrane protein 1 (LAMP1) were level p62 upregulated both cell models, suggesting autophagy inhibited, which restored treatment. In addition, transcription factor EB (TFEB) major regulator lysosome biogenesis TFEB decreased steatosis hepatocytes, could ameliorated These results revealed beneficial effects on via TFEB-mediated autophagy.

Language: Английский

Citations

0
EPSD 2.0: An Updated Database of Protein Phosphorylation Sites across Eukaryotic Species DOI Creative Commons
Miaomiao Chen, Yujie Gou,

Lei Ming

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 15, 2025

Abstract As one of the most crucial post-translational modifications (PTMs), protein phosphorylation regulates a broad range biological processes in eukaryotes. Biocuration, integration and annotation reported events will deliver valuable resource for community. Here, we present an updated database, eukaryotic site database 2.0 (EPSD 2.0), which includes 2,769,163 experimentally identified sites (p-sites) 362,707 phosphoproteins from 223 From literature, 873,718 new p-sites through high-throughput phosphoproteomic research were first collected, 1,078,888 original phosphopeptides together with primary references reserved. Then, this dataset was merged into EPSD 1.0, comprising 1,616,804 within 209,326 proteins across 68 organisms [1]. We also integrated 362,190 additional known 10 public databases. After redundancy clearance, manually re-checked each p-site annotated 88,074 functional 32,762 p-sites, covering 58 types downstream effects on phosphoproteins, regulatory impacts 107 processes. In addition, 8 model meticulously utilizing information supplied by 100 external platforms encompassing 15 areas. These areas included kinase/phosphatase, transcription regulators, three-dimensional structures, physicochemical characteristics, genomic variations, descriptions, domains, molecular interactions, drug-target associations, disease-related data, orthologs, transcript expression levels, proteomics, subcellular localization, pathways. expect that become useful supporting comprehensive studies The is freely accessible online at https://epsd.biocuckoo.cn/ .

Language: Английский

Citations

0
JOSD2 inhibits angiotensin II-induced vascular remodeling by deubiquitinating and stabilizing SMAD7 DOI Creative Commons

Sirui Shen,

Zhuqi Huang,

Yukai Yang

et al.

Acta Pharmacologica Sinica, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 20, 2025

Language: Английский

Citations

0
Sulfur Dioxide Alleviates Aortic Dissection Through Inhibiting Vascular Smooth Muscle Cell Phenotype Switch, Migration, and Proliferation via miR-184-3p/Cyp26b1 Axis DOI
Jie He, Kan Huang, Xiaoping Fan

et al.

Antioxidants and Redox Signaling, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 20, 2025

Aims: Abnormal migration and proliferation of vascular smooth muscle cells (VSMCs) are considered early events in the onset thoracic aortic dissection (TAD). Endogenous sulfur dioxide (SO2), primarily produced by aspartate aminotransferase (AAT1) mammals, has been reported to inhibit VSMCs. However, role SO2 development TAD remains unclear. Results: production was decreased samples from patients with TAD. Supplementation ameliorated β-aminopropionitrile-induced injury mice. Increasing expression pathway might reverse abnormal migration, proliferation, phenotypic switching MicroRNA sequencing revealed miR-184-3p as miRNA most significant increased level after AAT1 knockdown, Cyp26b1 predicted be its potential target. A decrease resulted reduced expression, impairing VSMCs function, while restoring inhibitors could improve function. Innovation: This research extends application endogenous diseases elucidates regulatory network, highlighting a target for clinical practice. Conclusion: inhibits progression via miR-184-3p/Cyp26b1 axis. Antioxid. Redox Signal. 00, 000-000.

Language: Английский

Citations

0
Phospholipase C epsilon 1 as a therapeutic target in cardiovascular diseases DOI Creative Commons
Jie Wang, Ting Gao, Dongmei Zhang

et al.

Journal of Advanced Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
Targeting the S100A9/P38 MAPK/HSPB1 axis as a novel approach for aortic dissection therapy DOI

Likang Ma,

Linfeng Xie, Qingsong Wu

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 149, P. 114225 - 114225

Published: Feb. 3, 2025

Language: Английский

Citations

0