SIRT1 pharmacological activation rescues vascular dysfunction and prevents thrombosis in MTHFR deficiency

Carrizzo, Albino; Iside, Concetta; Nebbioso, Angela; Carafa, Vincenzo; Damato, Antonio L.; Sciarretta, Sebastiano; Frati, Giacomo; Nonno, Flavio Di; Valenti, Valentina; Ciccarelli, Michele; Venturini, Eleonora; Scioli, Mariarosaria; Pietro, Paola Di; Bucci, Tommaso; Giudice, Valentina; Storto, Marianna; Serio, Bianca; Puca, Annibale Alessandro; Giugliano, Giuseppe; Trimarco, Valentina; Izzo, Raffaele; Trimarcö, Bruno; Selleri, Carmine; Altucci, Lucia; Vecchione, Carmine

doi:10.1007/s00018-022-04429-5

Cited by 16 publications

(11 citation statements)

References 45 publications

(51 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Elevated levels of serum homocysteine mainly cause a decrease in the antithrombotic effect of the vessel wall, increasing the risk of stroke ( 37 ). In contrast, aneurysm formation and rupture are mainly considered to be related to damage to the vessel wall and the release of inflammatory factors, and may not be related to the level of homocysteine.…”

Section: Discussionmentioning

confidence: 99%

Hyperhomocysteinemia and intracranial aneurysm: A mendelian randomization study

Zhang²,

Mao³

et al. 2022

Front. Neurol.

View full text Add to dashboard Cite

ObjectiveTo investigate the link between genetic variants associated with plasma homocysteine levels and risk of intracranial aneurysm (IA) using two-sample Mendelian randomization.MethodsWe used single-nucleotide polymorphisms associated with human plasma homocysteine levels as instrumental variables for the primary analysis in a genome-wide association study of 44,147 subjects of European ancestry. Summary-level statistics were obtained for 79,429 individuals, including 7,495 IA cases and 71,934 controls. To enhance validity, five different Mendelian randomization methods (MR-Egger, weighted median, inverse variance weighted, simple mode, and weighted mode) were used for the analyses.ResultsThe inverse variance weighted analysis method produced P-values of 0.398 for aneurysmal subarachnoid hemorrhage [odds ratio (OR): 1.104; 95% confidence interval (CI): 0.878–1.387], 0.246 for IA (OR: 1.124; 95% CI: 0.923–1.368), and 0.644 for unruptured IA (OR: 1.126; 95% CI: 0.682–1.858). The MR-Egger analysis showed no association between IAs and homocysteine, with all P > 0.05.ConclusionUsing gene-related instrumental variables, the Mendelian randomization analyses demonstrated a lack of an association between plasma homocysteine levels and IAs or aneurysmal subarachnoid hemorrhage.

show abstract

Section: Discussionmentioning

confidence: 99%

Hyperhomocysteinemia and intracranial aneurysm: A mendelian randomization study

Zhang²,

Mao³

et al. 2022

Front. Neurol.

View full text Add to dashboard Cite

show abstract

“…General Aspects Regarding Sirtuins 2.1.1. SIRT1 Among the sirtuin family members, SIRT1 has been extensively studied and is expressed in a wide range of human tissues, including the brain, liver, muscle, endothelium, pancreas, and adipose tissue [20][21][22]. In the central nervous system, SIRT1 is widely expressed in neurons of the cortex, hippocampus, cerebellum, and thalamus [23,24].…”

Section: Sirtuins In Ischemic Strokementioning

confidence: 99%

Sirtuins: Promising Therapeutic Targets to Treat Ischemic Stroke

et al. 2023

View full text Add to dashboard Cite

Stroke is a major cause of mortality and disability globally, with ischemic stroke (IS) accounting for over 80% of all stroke cases. The pathological process of IS involves numerous signal molecules, among which are the highly conserved nicotinamide adenine dinucleotide (NAD+)-dependent enzymes known as sirtuins (SIRTs). SIRTs modulate various biological processes, including cell differentiation, energy metabolism, DNA repair, inflammation, and oxidative stress. Importantly, several studies have reported a correlation between SIRTs and IS. This review introduces the general aspects of SIRTs, including their distribution, subcellular location, enzyme activity, and substrate. We also discuss their regulatory roles and potential mechanisms in IS. Finally, we describe the current therapeutic methods based on SIRTs, such as pharmacotherapy, non-pharmacological therapeutic/rehabilitative interventions, epigenetic regulators, potential molecules, and stem cell-derived exosome therapy. The data collected in this study will potentially contribute to both clinical and fundamental research on SIRTs, geared towards developing effective therapeutic candidates for future treatment of IS.

show abstract

“…The detailed protocol is provided in [20]. The antibodies used were Anti-KCTD1 (LS-C260993, LS-Bio, Seattle, WA, USA), Anti-Flag (MA1-91878, Thermo Fisher), anti-IKβα (662402, Biolegend, USA), anti-β-catenin (Sc-7963, SantaCruz), and anti-β-actin (ab11004, Abcam, UK) as loading controls.…”

Section: Western Blotting Analysismentioning

confidence: 99%

A Comprehensive Analysis of the Expression Profiles of KCTD Proteins in Acute Lymphoblastic Leukemia: Evidence of Selective Expression of KCTD1 in T-ALL

Buono¹,

Iside²,

Pecoraro³

et al. 2023

JCM

Self Cite

View full text Add to dashboard Cite

Acute leukemia is the most common pediatric cancer. In most cases, this disease results from the malignant transformation of either the B-cell (B-ALL) or, less frequently, T-cell progenitors (T-ALL). Recently, a marked overexpression of KCTD15, a member of the emerging class of the potassium (K) channel tetramerization domain-containing proteins (KCTDs) has been detected in both patients and continuous cell lines as in vitro model systems. Because there is growing evidence of the key, yet diversified, roles played by KCTDs in cancers, we here report an exhaustive analysis of their expression profiles in both B-ALL and T-ALL patients. Although for most KCTDs, no significant alterations were found in these pathological states, for some members of the family, significant up- and down-regulations were detected in comparison with the values found in healthy subjects in the transcriptome analysis. Among these, particularly relevant is the upregulation of the closely related KCTD1 and KCTD15 in T-ALL patients. Interestingly, KCTD1 is barely expressed in both unaffected controls and B-ALL patients. Therefore, not only does this analysis represent the first study in which the dysregulation of all KCTDs is simultaneously evaluated in specific pathological contexts, but it also provides a promising T-ALL biomarker that could be suitable for clinical applications.

show abstract

SIRT1 pharmacological activation rescues vascular dysfunction and prevents thrombosis in MTHFR deficiency

Cited by 16 publications

References 45 publications

Hyperhomocysteinemia and intracranial aneurysm: A mendelian randomization study

Hyperhomocysteinemia and intracranial aneurysm: A mendelian randomization study

Sirtuins: Promising Therapeutic Targets to Treat Ischemic Stroke

A Comprehensive Analysis of the Expression Profiles of KCTD Proteins in Acute Lymphoblastic Leukemia: Evidence of Selective Expression of KCTD1 in T-ALL

Contact Info

Product

Resources

About