Nicotinamide Phosphoribosyltransferase in Smooth Muscle Cells Maintains Genome Integrity, Resists Aortic Medial Degeneration, and Is Suppressed in Human Thoracic Aortic Aneurysm Disease

Watson, Alanna; Zhang, Nong; Yin, Hao; O’Neil, Caroline; Fox, Stephanie A.; Balint, Brittany; Guo, Lina; Léo, Oberdan; Chu, Michael; Gros, Robert; Pickering, J. Geoffrey

doi:10.1161/circresaha.116.310022

Cited by 57 publications

(56 citation statements)

References 45 publications

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“…Advances in genetics, molecular and cellular biology, medical imaging, and bioengineering have advanced our understanding of this disease, yet clear pharmacotherapy remains elusive. The paper by Watson and colleagues 5 further highlights the complexity of this disease process. We concur that increased attention should be directed to the NAMPT-NAD + control system in studying thoracic aortopathy, but with broad appreciation of its myriad direct and indirect temporal effects on cell vitality and thus matrix integrity.…”

Section: Resultsmentioning

confidence: 98%

“…A striking finding in the pathologic aortas of the AngII-infused VSMC- Nampt deficient mice was loss of VSMCs 5 . Although TUNEL staining could not document VSMC apoptosis after 28 days of infusion, the evident senescence and yet dramatic loss of medial cells suggest that many VSMCs could have undergone apoptosis earlier.…”

Section: Vsmc Vitalitymentioning

confidence: 98%

“…Watson and colleagues 5 report provocative findings in human tissue that correlate the NAMPT-NAD + control system with thoracic aortic dilatation. Among other observations, the NAMPT promoter was hypermethylated in situ and in vitro in VSMCs from patients with dilated ascending aortopathy, and lower levels of NAMPT correlated with increased DNA breaks.…”

Section: Nampt Genome Integrity and Aortopathymentioning

confidence: 99%

“…Both of these studies report localized accumulations of mucoid material, similar to that in human histopathology and a potential initiator of dissection 7 . Watson et al 5 conclude that aortic integrity depends on an intrinsic NAMPT-NAD + system, which when compromised results in unrepaired DNA damage and VSMC senescence.…”

Section: Nampt Genome Integrity and Aortopathymentioning

confidence: 99%

“…A corollary, therefore, is that NAMPT deficiency could increase nicotinamide and thereby decrease VSMC contractility. Hence, despite some controversy 4,5 , the NAMPT-NAD + control system may influence actomyosin activity directly and indirectly and thereby affect VSMC contraction-mediated ECM integrity.…”

Section: Ecm Integrity and Vsmc Contractilitymentioning

confidence: 99%

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Aging, Smooth Muscle Vitality, and Aortic Integrity

Humphrey

Milewicz

2017

Circulation Research

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Advances in medical genetics and imaging have resulted in a significant increase in the number of diagnosed thoracic aortic aneurysms. Recent findings establish a link between diminished nicotinamide phosphoribosyltransferase (NAMPT) and compromised smooth muscle cell vitality in aortic dilatation. These findings have myriad implications given the diverse roles of NAMPT, which is central to the production of nicotinamide adenine dinucleotide (NAD+), and thus ATP production, as well the activity of multiple NAD+ consuming proteins. Given its central role in vascular cell vitality and thus matrix integrity, further attention should be directed to the NAMPT-NAD+ control system in thoracic aortopathy.

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Section: Resultsmentioning

confidence: 98%

Section: Vsmc Vitalitymentioning

confidence: 98%

Section: Nampt Genome Integrity and Aortopathymentioning

confidence: 99%

Section: Nampt Genome Integrity and Aortopathymentioning

confidence: 99%

Section: Ecm Integrity and Vsmc Contractilitymentioning

confidence: 99%

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Aging, Smooth Muscle Vitality, and Aortic Integrity

Humphrey

Milewicz

2017

Circulation Research

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Genetics of Aortic Diseases

DieterJr.

Raabe

2019

Diseases of the Aorta

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Telomere Length: Implications for Atherogenesis

Yin

Pickering

2023

Curr Atheroscler Rep

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Purpose of Review The purpose of the study is to explore the evidence linking telomere length with atherosclerotic ischemic disease. Recent Findings There has been a recent expansion in strategies for measuring telomere length, including analyzing genome sequence data and capitalizing on genomic loci that associate with telomere length. These, together with more established approaches, have been used to generate a more complete picture of telomere length relationships with ischemic disease. Whereas earlier meta-analyses suggested an association between short leukocyte telomeres and ischemic disease, several recent large population studies now provide particularly compelling data, including an association with cardiovascular mortality. In addition, whether short leukocyte telomeres might be causally related to ischemic disease has been interrogated using Mendelian randomization strategies, which point to shorter leukocyte telomeres as a determining risk factor. Importantly however, the wide, interindividual variability in telomere length still means that a single assessment of leukocyte telomere length in an individual does not reliably report on a biological aging process. In this regard, recent multi-tissue analyses of telomere length dynamics are providing both new mechanistic insights into how telomere length and shortening rates may participate in atherogenesis and risk prediction opportunities. Summary The balance of evidence indicates that short leukocyte telomeres confer a risk for atherosclerotic cardiovascular disease. Moreover, an integrated analysis of telomere lengths in leukocytes and other tissues may provide a window into individualized telomere dynamics, raising new prospects for risk management.

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Nicotinamide Phosphoribosyltransferase in Smooth Muscle Cells Maintains Genome Integrity, Resists Aortic Medial Degeneration, and Is Suppressed in Human Thoracic Aortic Aneurysm Disease

Abstract: The aortic media depends on an intrinsic NAD fueling system to protect against DNA damage and premature SMC senescence, with relevance to human thoracic aortopathy.

Cited by 57 publications

References 45 publications

Aging, Smooth Muscle Vitality, and Aortic Integrity

Aging, Smooth Muscle Vitality, and Aortic Integrity

Genetics of Aortic Diseases

Telomere Length: Implications for Atherogenesis

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