Redox Dysregulation of Vascular Smooth Muscle Sirtuin-1 in Thoracic Aortic Aneurysm in Marfan Syndrome

Enkhjargal, Budbazar; S, Leon; Tsukahara, Yusuke; Liu, Hanxiao; Huangfu, Yuhao; Yu, Yongguo; Seabra, Paula Mannan; Xiao, Yang; Goodman, Jena; Wan, Xueping; Chitalia, Vipul C.; Han, Jing‐Yan; Seta, Francesca

doi:10.1161/atvbaha.123.319145

Cited by 3 publications

(3 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Fbn1 mgR/mgR mice: These mice are another model of Marfan syndrome and are the second most commonly used genetic model in TAA [49,[89][90][91][92][93][94][95][96]. The Fbn1 mgR allele is generated by insertion of the PGKneo expression cassette into an intron region of the Fbn1 gene without loss of the Fbn1 exon sequence [97].…”

Section: Genetic Taa Models In Rodentsmentioning

confidence: 99%

Animal Models, Pathogenesis, and Potential Treatment of Thoracic Aortic Aneurysm

Wang,

Panicker,

Anesi

et al. 2024

IJMS

View full text Add to dashboard Cite

Thoracic aortic aneurysm (TAA) has a prevalence of 0.16–0.34% and an incidence of 7.6 per 100,000 person-years, accounting for 1–2% of all deaths in Western countries. Currently, no effective pharmacological therapies have been identified to slow TAA development and prevent TAA rupture. Large TAAs are treated with open surgical repair and less invasive thoracic endovascular aortic repair, both of which have high perioperative mortality risk. Therefore, there is an urgent medical need to identify the cellular and molecular mechanisms underlying TAA development and rupture to develop new therapies. In this review, we summarize animal TAA models including recent developments in porcine and zebrafish models: porcine models can assess new therapeutic devices or intervention strategies in a large mammal and zebrafish models can employ large-scale small-molecule suppressor screening in microwells. The second part of the review covers current views of TAA pathogenesis, derived from recent studies using these animal models, with a focus on the roles of the transforming growth factor-beta (TGFβ) pathway and the vascular smooth muscle cell (VSMC)-elastin-contractile unit. The last part discusses TAA treatment options as they emerge from recent preclinical studies.

show abstract

Section: Genetic Taa Models In Rodentsmentioning

confidence: 99%

Animal Models, Pathogenesis, and Potential Treatment of Thoracic Aortic Aneurysm

Wang,

Panicker,

Anesi

et al. 2024

IJMS

View full text Add to dashboard Cite

show abstract

“…SIRT1, as a post‐translational regulator, plays a role in regulating various diseases including diabetes, cancer, cardiovascular diseases and neurodegenerative diseases 16,17 . Multiple studies have reported that SIRT1 expression is reduced in aortic dissection or aneurysm, and the upregulation of SIRT1 in endothelial cells or smooth muscle cells can block the occurrence of diseases by reducing cellular oxidative stress and inflammatory responses 18,19 …”

Section: Introductionmentioning

confidence: 99%

“… 16 , 17 Multiple studies have reported that SIRT1 expression is reduced in aortic dissection or aneurysm, and the upregulation of SIRT1 in endothelial cells or smooth muscle cells can block the occurrence of diseases by reducing cellular oxidative stress and inflammatory responses. 18 , 19 …”

Section: Introductionmentioning

confidence: 99%

miR‐485‐3p targets SIRT1 in vascular smooth muscle cells mediating the occurrence of aortic dissection

Xie,

Qiu

et al. 2024

J Cellular Molecular Medi

View full text Add to dashboard Cite

Studies have demonstrated a close correlation between MicroRNA and the occurrence of aortic dissection (AD). However, the molecular mechanisms underlying this relationship have not been fully elucidated and further exploration is still required. In this study, we found that miR‐485‐3p was significantly upregulated in human aortic dissection tissues. Meanwhile, we constructed in vitro AD models in HAVSMCs, HAECs and HAFs and found that the expression of miR‐485‐3p was increased only in HAVSMCs. Overexpression or knockdown of miR‐485‐3p in HAVSMCs could regulate the expression of inflammatory cytokines IL1β, IL6, TNF‐α, and NLRP3, as well as the expression of apoptosis‐related proteins BAX/BCL2 and Cleaved caspase3/Caspase3. In the in vivo AD model, we have observed that miR‐485‐3p regulates vascular inflammation and apoptosis, thereby participating in the modulation of AD development in mice. Based on target gene prediction, we have validated that SIRT1 is a downstream target gene of miR‐485‐3p. Furthermore, by administering SIRT1 agonists and inhibitors to mice, we observed that the activation of SIRT1 alleviates vascular inflammation and apoptosis, subsequently reducing the incidence of AD. Additionally, functional reversal experiments revealed that overexpression of SIRT1 in HAVSMCs could reverse the cell inflammation and apoptosis mediated by miR‐485‐3p. Therefore, our research suggests that miR‐485‐3p can aggravate inflammation and apoptosis in vascular smooth muscle cells by suppressing the expression of SIRT1, thereby promoting the progression of aortic dissection.

show abstract

The Role of S-Glutathionylation in Health and Disease: A Bird’s Eye View

Federici,

Masulli,

De Laurenzi

et al. 2024

Nutrients

View full text Add to dashboard Cite

Protein glutathionylation is a reversible post-translational modification that involves the attachment of glutathione to cysteine residues. It plays a role in the regulation of several cellular processes and protection against oxidative damage. Glutathionylation (GS-ylation) modulates protein function, inhibits or enhances enzymatic activity, maintains redox homeostasis, and shields several proteins from irreversible oxidative stress. Aberrant GS-ylation patterns are thus implicated in various diseases, particularly those associated with oxidative stress and inflammation, such as cardiovascular diseases, neurodegenerative disorders, cancer, and many others. Research in the recent years has highlighted the potential to manipulate protein GS-ylation for therapeutic purposes with strategies that imply both its enhancement and inhibition according to different cases. Moreover, it has become increasingly evident that monitoring the GS-ylation status of selected proteins offers diagnostic potential in different diseases. In this review, we try to summarize recent research in the field with a focus on our current understanding of the molecular mechanisms related to aberrant protein GS-ylation.

show abstract

Redox Dysregulation of Vascular Smooth Muscle Sirtuin-1 in Thoracic Aortic Aneurysm in Marfan Syndrome

Cited by 3 publications

References 55 publications

Animal Models, Pathogenesis, and Potential Treatment of Thoracic Aortic Aneurysm

Animal Models, Pathogenesis, and Potential Treatment of Thoracic Aortic Aneurysm

miR‐485‐3p targets SIRT1 in vascular smooth muscle cells mediating the occurrence of aortic dissection

The Role of S-Glutathionylation in Health and Disease: A Bird’s Eye View

Contact Info

Product

Resources

About