Combination of Genomic and Transcriptomic Approaches Highlights Vascular and Circadian Clock Components in Multiple Sclerosis

Scapoli, Chiara; Ziliotto, Nicole; Lunghi, Barbara; Menegatti, Erica; Salvi, Fabrizio; Zamboni, Paolo; Baroni, Marcello; Mascoli, Francesco; Bernardi, Francesco; Marchetti, Giovanna

doi:10.3390/ijms23010310

Cited by 9 publications

(7 citation statements)

References 97 publications

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“…Similarly, TF NUPR1 encoding nuclear protein 1 (Nupr1), a marker for phenotypic modulation (modSMCs) towards a fibroblast-like state, which was found to be activated in this study, also appeared in another single-cell transcriptomic profile of VSMC phenotypes [ 80 ]. PPARGC1A, a TF that was observed to be inhibited in this study, also appeared in another genomic and transcriptomic analysis highlighting the role of vascular changes in multiple sclerosis—mainly immune and inflammation-related pathologies mediating perivascular changes [ 81 ]. Since perivascular cuffing and perivascular inflammation are associated with arterial thrombosis [ 12 ], investigating the role of PPARGC1A will enhance the understanding of the molecular mechanism underlying early AVF failure.…”

Section: Future Perspectivesmentioning

confidence: 88%

Transcriptional and Epigenetic Factors Associated with Early Thrombosis of Femoral Artery Involved in Arteriovenous Fistula

Rai

Agrawal

2022

Proteomes

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Arteriovenous fistulas (AVFs), created for hemodialysis in end-stage renal disease patients, mature through the outward remodeling of the outflow vein. However, early thrombosis and chronic inflammation are detrimental to the process of AVF maturation and precipitate AVF maturation failure. For the successful remodeling of the outflow vein, blood flow through the fistula is essential, but early arterial thrombosis attenuates this blood flow, and the vessels become thrombosed and stenosed, leading to AVF failure. The altered expression of various proteins involved in maintaining vessel patency or thrombosis is regulated by genes of which the expression is regulated by transcription factors and microRNAs. In this study, using thrombosed and stenosed arteries following AVF creation, we delineated transcription factors and microRNAs associated with differentially expressed genes in bulk RNA sequencing data using upstream and causal network analysis. We observed changes in many transcription factors and microRNAs that are involved in angiogenesis; vascular smooth muscle cell proliferation, migration, and phenotypic changes; endothelial cell function; hypoxia; oxidative stress; vessel remodeling; immune responses; and inflammation. These factors and microRNAs play a critical role in the underlying molecular mechanisms in AVF maturation. We also observed epigenetic factors involved in gene regulation associated with these molecular mechanisms. The results of this study indicate the importance of investigating the transcriptional and epigenetic regulation of AVF maturation and maturation failure and targeting factors precipitating early thrombosis and stenosis.

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Section: Future Perspectivesmentioning

confidence: 88%

Transcriptional and Epigenetic Factors Associated with Early Thrombosis of Femoral Artery Involved in Arteriovenous Fistula

Rai

Agrawal

2022

Proteomes

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“…Furthermore, differential expression and frequency of low-frequency variants were observed in MS families for six genes involved in circadian entrainment/rhythm. 101 The expression of Per2 in the liver showed altered circadian rhythms in an animal model of MS. 102…”

Section: Clock Genes In Msmentioning

confidence: 99%

“…A specific genotype of PER3, a clock gene controlling circadian rhythm and sleep, is associated with accelerated MS disease course 100 (Figure 2). Furthermore, differential expression and frequency of low‐frequency variants were observed in MS families for six genes involved in circadian entrainment/rhythm 101 . The expression of Per2 in the liver showed altered circadian rhythms in an animal model of MS 102 …”

Section: Circadian Disturbances In Msmentioning

confidence: 99%

Multiple sclerosis and circadian rhythms: Can diet act as a treatment?

2023

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Multiple sclerosis (MS) is an autoimmune inflammatory and neurodegenerative disease of the central nervous system (CNS) with increasing incidence and prevalence. MS is associated with inflammatory and metabolic disturbances that, as preliminary human and animal data suggest, might be mediated by disruption of circadian rhythmicity. Nutrition habits can influence the risk for MS, and dietary interventions may be effective in modulating MS disease course.Chronotherapeutic approaches such as time-restricted eating (TRE) may benefit people with MS by stabilizing the circadian clock and restoring immunological and metabolic rhythms, thus potentially counteracting disease progression. This review provides a summary of selected studies on dietary intervention in MS, circadian rhythms, and their disruption in MS, including clock gene variations, circadian hormones, and retino-hypothalamic tract changes. Furthermore, we present studies that reported diurnal variations in MS, which might result from circadian disruption. And lastly, we suggest how chrononutritive approaches like TRE might counteract MS disease activity.

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“…Additionally, these findings provide evidence for the presence of pleiotropic loci among MS and cardiovascular comorbidities. LEF1 and SMARCA4, both members of the WNT/beta-catenin pathway, have been linked to vascular remodeling, post-stroke angiogenesis, and cardio-cerebral-peripheral vascular diseases 80 , 81 .…”

Section: Pathophysiology Of Vascular Msmentioning

confidence: 99%

Vascular multiple sclerosis: addressing the pathogenesis, genetics, pro-angiogenic factors, and vascular abnormalities, along with the role of vascular intervention

Prajjwal,

Shree,

Das

et al. 2023

Annals of Medicine &Amp; Surgery

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Dysfunction in the epithelium, breakdown of the blood-brain barrier, and consequent leukocyte and T-cell infiltration into the central nervous system define Vascular Multiple Sclerosis. Multiple Sclerosis (MS) affects around 2.5 million individuals worldwide, is the leading cause of neurological impairment in young adults, and can have a variety of progressions and consequences. Despite significant discoveries in immunology and molecular biology, the root cause of MS is still not fully understood, as do the immunological triggers and causative pathways. Recent research into vascular anomalies associated with MS suggests that a vascular component may be pivotal to the etiology of MS, and there can be actually a completely new entity in the already available classification of multiple sclerosis, that can be called ‘Vascular multiple sclerosis’. Unlike the usual other causes of MS, Vascular MS is not dependent on autoimmune pathophysiologic mechanisms, instead, it is caused due to the blood vessels pathology. This review aims to thoroughly analyze existing information and updates about the scattered available findings of genetics, pro-angiogenetic factors, and vascular abnormalities in this important spectrum, the vascular facets of multiple sclerosis.

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Combination of Genomic and Transcriptomic Approaches Highlights Vascular and Circadian Clock Components in Multiple Sclerosis

Cited by 9 publications

References 97 publications

Transcriptional and Epigenetic Factors Associated with Early Thrombosis of Femoral Artery Involved in Arteriovenous Fistula

Transcriptional and Epigenetic Factors Associated with Early Thrombosis of Femoral Artery Involved in Arteriovenous Fistula

Multiple sclerosis and circadian rhythms: Can diet act as a treatment?

Vascular multiple sclerosis: addressing the pathogenesis, genetics, pro-angiogenic factors, and vascular abnormalities, along with the role of vascular intervention

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