The NRF2/ID2 Axis in Vascular Smooth Muscle Cells: Novel Insights into the Interplay between Vascular Calcification and Aging DOI Creative Commons

Mulin Xu,

Xiuxian Wei, Jinli Wang

et al.

Aging and Disease, Journal Year: 2024, Volume and Issue: unknown, P. 0 - 0

Published: Jan. 1, 2024

Vascular calcification (VC) increases with age and markedly exacerbates the risk of cardiovascular morbidity mortality. However, effective pharmaceutical interventions are lacking molecular mechanisms linking aging to VC remain elusive. This study explored role nuclear factor erythroid 2-related 2 (NRF2) in age-associated VC, specifically focusing on vascular smooth muscle cell (VSMC) senescence. Using a chronologically mouse model, we noted significant decline expression NRF2 aged mice aortas, coinciding increased VC. Administering activators effectively reduced calcification. By establishing adenine-and vitamin D-induced models VSMC-specific Nrf2 knockout (Nrf2SMCKO) mice, there was an increase VSMC Aortic rings primary VSMCs from Nrf2SMCKO also showed under high-phosphate conditions. Furthermore, overexpression inhibited decreased senescence osteogenic phenotype, whereas silencing aggravated Transcriptome RNA-seq analysis aortas control revealed that inhibitor DNA binding (Id2) is core downstream gene NRF2. Id2 alleviated NRF2 knockdown-induced senescence, while negated protective effects Moreover, results dual luciferase reporter assay indicated promotes transcriptional activity promoter region. emphasizes critical age-related dysfunction nexus between The NRF2-ID2 axis has been proposed as promising therapeutic target for reducing mitigating diseases.

Language: Английский

A pH-responsive PROTAC-based nanosystem triggers tumor-specific ferroptosis to construct in situ tumor vaccines DOI Creative Commons
Linghong Huang, Xin‐Yuan Sun, Qinhua Zuo

et al.

Materials Today Bio, Journal Year: 2025, Volume and Issue: 31, P. 101523 - 101523

Published: Jan. 25, 2025

Language: Английский

Citations

1
Bioinformatics analysis of ferroptosis-related hub genes and immunoinfiltration in myocardial ischemia/reperfusion following heart transplantation DOI Creative Commons
Yuxi Zhang, Qiao Tang, Jiahui Cui

et al.

BMC Cardiovascular Disorders, Journal Year: 2025, Volume and Issue: 25(1)

Published: Jan. 10, 2025

Ischemia/reperfusion (I/R) is an inevitable pathophysiological process during heart transplantation, and ferroptosis important pathogenic mechanism. Unlike other modes of cell death, depends on the accumulation iron within oxidative degradation polyunsaturated fatty acids. Dysregulation this pathway has been linked to progression multiple pathological conditions, making it attractive target for therapeutic intervention. Therefore, study aims explore effect I/R transplantation. GEO2R was applied identify differentially expressed genes (DEGs) obtained from GSE50884 data, which involved in And ferroptosis-related DEGs (FRDEGs) were screened by venn diagram with downloaded FerDb database. FRDEGs enriched analyzed GO KEGG, hub related Cytoscape software database STRING. Additionally, considering relationship between immunity, CIBERSORTx analyze infiltration 22 kinds immune cells correlation each expression also discussed. Finally, mouse model transplantation constructed, verified RT-qPCR western blot. 12 identified out 327 GSE50844, mainly pathways. Three (SLC7A11, PSAT1, ASNS) degree algorithm cytohubba plug-in. Immunoinfiltration analysis showed that 16 changed, score higher than without I/R. In addition, exhibited significant Eosinophils, NK resting, Dendritic activated T CD4 memory activated. We SLC7A11, PSAT1 ASNS normal tissues using blot models I/R, companied aggravated involved. short, injury infiltration. provide targets ameliorating

Language: Английский

Citations

0
The NRF2/ID2 Axis in Vascular Smooth Muscle Cells: Novel Insights into the Interplay between Vascular Calcification and Aging DOI Open Access

Mulin Xu,

Xiuxian Wei, Jinli Wang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 3, 2024

Abstract OBJECTIVE Vascular calcification (VC) significantly contributes to cardiovascular morbidity and mortality escalates with age. However, effective pharmaceutical interventions are lacking, the molecular mechanisms linking aging VC remain elusive. This study explores role of nuclear factor erythroid 2-related 2 (NRF2) in VC, specifically focusing on interplay between vascular senescence oxidative stress (OS). APPROACH AND RESULTS Using a chronological mouse model, we noted significant decline expression activity Nrf2 aortas aged mice, coinciding increased medial VC. Administering NRF2 activators effectively reduced this calcification. In smooth muscle cell (VSMC)-specific knockout ( SMCKO ) models, created using adenine Vitamin D, there was an increase calcium deposition within aortic layer, alongside heightened VSMC OS. Furthermore, exacerbated rings primary VSMCs high-phosphate conditions, while overexpression inhibited by alleviating RNAseq analysis from control mice highlighted downstream regulator Inhibitor DNA Binding (ID2). Our results show that levels lead senescence, characterized p16 diminished ID2 expression. Inhibiting negated NRF2’s protective effects against CONCLUSION emphasizes critical dysfunction nexus OS, It proposes NRF2-ID2 axis as promising therapeutic target for reducing mitigating age-related diseases. Highlights Decline is linked aging. VSMC-specific causes remarkable exacerbation arterial alleviates inhibiting senescence.

Language: Английский

Citations

0
The NRF2/ID2 Axis in Vascular Smooth Muscle Cells: Novel Insights into the Interplay between Vascular Calcification and Aging DOI Creative Commons

Mulin Xu,

Xiuxian Wei, Jinli Wang

et al.

Aging and Disease, Journal Year: 2024, Volume and Issue: unknown, P. 0 - 0

Published: Jan. 1, 2024

Vascular calcification (VC) increases with age and markedly exacerbates the risk of cardiovascular morbidity mortality. However, effective pharmaceutical interventions are lacking molecular mechanisms linking aging to VC remain elusive. This study explored role nuclear factor erythroid 2-related 2 (NRF2) in age-associated VC, specifically focusing on vascular smooth muscle cell (VSMC) senescence. Using a chronologically mouse model, we noted significant decline expression NRF2 aged mice aortas, coinciding increased VC. Administering activators effectively reduced calcification. By establishing adenine-and vitamin D-induced models VSMC-specific Nrf2 knockout (Nrf2SMCKO) mice, there was an increase VSMC Aortic rings primary VSMCs from Nrf2SMCKO also showed under high-phosphate conditions. Furthermore, overexpression inhibited decreased senescence osteogenic phenotype, whereas silencing aggravated Transcriptome RNA-seq analysis aortas control revealed that inhibitor DNA binding (Id2) is core downstream gene NRF2. Id2 alleviated NRF2 knockdown-induced senescence, while negated protective effects Moreover, results dual luciferase reporter assay indicated promotes transcriptional activity promoter region. emphasizes critical age-related dysfunction nexus between The NRF2-ID2 axis has been proposed as promising therapeutic target for reducing mitigating diseases.

Language: Английский

Citations

0