Association of single nucleotide polymorphisms in the NRF2 promoter with vascular stiffness with aging

Pulse wave velocity (PWV), an indicator of vascular stiffness, increases with age and is increasingly recognized as an independent risk factor for cardiovascular disease (CVD). Although many mechanical and chemical factors underlie the stiffness of the elastic artery, genetic risk factors related to...

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Published inPloS one Vol. 15; no. 8; p. e0236834
Main Authors Shimizu, Sunao, Mimura, Junsei, Hasegawa, Takanori, Shimizu, Eigo, Imoto, Seiya, Tsushima, Michiko, Kasai, Shuya, Yamazaki, Hiromi, Ushida, Yusuke, Suganuma, Hiroyuki, Tomita, Hirofumi, Yamamoto, Masayuki, Nakaji, Shigeyuki, Itoh, Ken
Format Journal Article
LanguageEnglish
Published San Francisco Public Library of Science 11.08.2020
Public Library of Science (PLoS)
Subjects
Age
Aging
Aging (Biology)
Alleles
Ankle
Arteriosclerosis
Atherosclerosis
Biology and Life Sciences
Biomedical research
Blood pressure
Cardiology
Cardiovascular disease
Cardiovascular diseases
Diabetes
Endothelium
Evaluation
Funding
Gene expression
Genetic aspects
Genomes
Health aspects
Health promotion
Health risks
Heart diseases
Homeostasis
Life sciences
Mechanical properties
Medical research
Medicine
Medicine and Health Sciences
Multivariate analysis
Nephrology
NRF2 protein
Nucleotides
Oxidative stress
Physical Sciences
Physiological aspects
Proteins
Public health
Research and Analysis Methods
Risk analysis
Risk factors
Senescence
Shear stress
Single nucleotide polymorphisms
Single-nucleotide polymorphism
Stiffness
Transcription factors
University graduates
Vascular resistance
Veins & arteries
Wave velocity
Japan
Online AccessGet full text

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Abstract Pulse wave velocity (PWV), an indicator of vascular stiffness, increases with age and is increasingly recognized as an independent risk factor for cardiovascular disease (CVD). Although many mechanical and chemical factors underlie the stiffness of the elastic artery, genetic risk factors related to age-dependent increases in PWV in apparently healthy people are largely unknown. The transcription factor nuclear factor E2 (NF-E2)-related factor 2 (Nrf2), which is activated by unidirectional vascular pulsatile shear stress or oxidative stress, regulates vascular redox homeostasis. Previous reports have shown that a SNP in the NRF2 gene regulatory region (-617C>A; hereafter called SNP-617) affects NRF2 gene expression such that the minor A allele confers lower gene expression compared to the C allele, and it is associated with various diseases, including CVD. We aimed to investigate whether SNP-617 affects vascular stiffness with aging in apparently healthy people. Analyzing wide-ranging data obtained from a public health survey performed in Japan, we evaluated whether SNP-617 affected brachial-ankle PWV (baPWV) in never-smoking healthy subjects (n = 642). We also evaluated the effects of SNP-617 on other cardiovascular and blood test measurements. We have shown that not only AA carriers (n = 55) but also CA carriers (n = 247) show arterial stiffness compared to CC carriers (n = 340). Furthermore, SNP-617 also affected blood pressure indexes such as systolic blood pressure and mean arterial pressure but not the ankle brachial pressure index, an indicator of atherosclerosis. Multivariate analysis showed that SNP-617 accelerates the incremental ratio of baPWV with age. This study is the first to show that SNP-617 affects the age-dependent increase in vascular stiffness. Our results indicate that low NRF2 activity induces premature vascular aging and could be targeted for the prevention of cardiovascular diseases associated with aging.
AbstractList Pulse wave velocity (PWV), an indicator of vascular stiffness, increases with age and is increasingly recognized as an independent risk factor for cardiovascular disease (CVD). Although many mechanical and chemical factors underlie the stiffness of the elastic artery, genetic risk factors related to age-dependent increases in PWV in apparently healthy people are largely unknown. The transcription factor nuclear factor E2 (NF-E2)-related factor 2 (Nrf2), which is activated by unidirectional vascular pulsatile shear stress or oxidative stress, regulates vascular redox homeostasis. Previous reports have shown that a SNP in the NRF2 gene regulatory region (-617C>A; hereafter called SNP-617) affects NRF2 gene expression such that the minor A allele confers lower gene expression compared to the C allele, and it is associated with various diseases, including CVD. We aimed to investigate whether SNP-617 affects vascular stiffness with aging in apparently healthy people. Analyzing wide-ranging data obtained from a public health survey performed in Japan, we evaluated whether SNP-617 affected brachial-ankle PWV (baPWV) in never-smoking healthy subjects (n = 642). We also evaluated the effects of SNP-617 on other cardiovascular and blood test measurements. We have shown that not only AA carriers (n = 55) but also CA carriers (n = 247) show arterial stiffness compared to CC carriers (n = 340). Furthermore, SNP-617 also affected blood pressure indexes such as systolic blood pressure and mean arterial pressure but not the ankle brachial pressure index, an indicator of atherosclerosis. Multivariate analysis showed that SNP-617 accelerates the incremental ratio of baPWV with age. This study is the first to show that SNP-617 affects the age-dependent increase in vascular stiffness. Our results indicate that low NRF2 activity induces premature vascular aging and could be targeted for the prevention of cardiovascular diseases associated with aging.
Pulse wave velocity (PWV), an indicator of vascular stiffness, increases with age and is increasingly recognized as an independent risk factor for cardiovascular disease (CVD). Although many mechanical and chemical factors underlie the stiffness of the elastic artery, genetic risk factors related to age-dependent increases in PWV in apparently healthy people are largely unknown. The transcription factor nuclear factor E2 (NF-E2)-related factor 2 (Nrf2), which is activated by unidirectional vascular pulsatile shear stress or oxidative stress, regulates vascular redox homeostasis. Previous reports have shown that a SNP in the NRF2 gene regulatory region (-617C>A; hereafter called SNP-617) affects NRF2 gene expression such that the minor A allele confers lower gene expression compared to the C allele, and it is associated with various diseases, including CVD. We aimed to investigate whether SNP-617 affects vascular stiffness with aging in apparently healthy people.PURPOSEPulse wave velocity (PWV), an indicator of vascular stiffness, increases with age and is increasingly recognized as an independent risk factor for cardiovascular disease (CVD). Although many mechanical and chemical factors underlie the stiffness of the elastic artery, genetic risk factors related to age-dependent increases in PWV in apparently healthy people are largely unknown. The transcription factor nuclear factor E2 (NF-E2)-related factor 2 (Nrf2), which is activated by unidirectional vascular pulsatile shear stress or oxidative stress, regulates vascular redox homeostasis. Previous reports have shown that a SNP in the NRF2 gene regulatory region (-617C>A; hereafter called SNP-617) affects NRF2 gene expression such that the minor A allele confers lower gene expression compared to the C allele, and it is associated with various diseases, including CVD. We aimed to investigate whether SNP-617 affects vascular stiffness with aging in apparently healthy people.Analyzing wide-ranging data obtained from a public health survey performed in Japan, we evaluated whether SNP-617 affected brachial-ankle PWV (baPWV) in never-smoking healthy subjects (n = 642). We also evaluated the effects of SNP-617 on other cardiovascular and blood test measurements.METHODSAnalyzing wide-ranging data obtained from a public health survey performed in Japan, we evaluated whether SNP-617 affected brachial-ankle PWV (baPWV) in never-smoking healthy subjects (n = 642). We also evaluated the effects of SNP-617 on other cardiovascular and blood test measurements.We have shown that not only AA carriers (n = 55) but also CA carriers (n = 247) show arterial stiffness compared to CC carriers (n = 340). Furthermore, SNP-617 also affected blood pressure indexes such as systolic blood pressure and mean arterial pressure but not the ankle brachial pressure index, an indicator of atherosclerosis. Multivariate analysis showed that SNP-617 accelerates the incremental ratio of baPWV with age.RESULTSWe have shown that not only AA carriers (n = 55) but also CA carriers (n = 247) show arterial stiffness compared to CC carriers (n = 340). Furthermore, SNP-617 also affected blood pressure indexes such as systolic blood pressure and mean arterial pressure but not the ankle brachial pressure index, an indicator of atherosclerosis. Multivariate analysis showed that SNP-617 accelerates the incremental ratio of baPWV with age.This study is the first to show that SNP-617 affects the age-dependent increase in vascular stiffness. Our results indicate that low NRF2 activity induces premature vascular aging and could be targeted for the prevention of cardiovascular diseases associated with aging.CONCLUSIONSThis study is the first to show that SNP-617 affects the age-dependent increase in vascular stiffness. Our results indicate that low NRF2 activity induces premature vascular aging and could be targeted for the prevention of cardiovascular diseases associated with aging.
Purpose Pulse wave velocity (PWV), an indicator of vascular stiffness, increases with age and is increasingly recognized as an independent risk factor for cardiovascular disease (CVD). Although many mechanical and chemical factors underlie the stiffness of the elastic artery, genetic risk factors related to age-dependent increases in PWV in apparently healthy people are largely unknown. The transcription factor nuclear factor E2 (NF-E2)-related factor 2 (Nrf2), which is activated by unidirectional vascular pulsatile shear stress or oxidative stress, regulates vascular redox homeostasis. Previous reports have shown that a SNP in the NRF2 gene regulatory region (−617C>A; hereafter called SNP−617) affects NRF2 gene expression such that the minor A allele confers lower gene expression compared to the C allele, and it is associated with various diseases, including CVD. We aimed to investigate whether SNP−617 affects vascular stiffness with aging in apparently healthy people. Methods Analyzing wide-ranging data obtained from a public health survey performed in Japan, we evaluated whether SNP−617 affected brachial-ankle PWV (baPWV) in never-smoking healthy subjects (n = 642). We also evaluated the effects of SNP−617 on other cardiovascular and blood test measurements. Results We have shown that not only AA carriers (n = 55) but also CA carriers (n = 247) show arterial stiffness compared to CC carriers (n = 340). Furthermore, SNP−617 also affected blood pressure indexes such as systolic blood pressure and mean arterial pressure but not the ankle brachial pressure index, an indicator of atherosclerosis. Multivariate analysis showed that SNP−617 accelerates the incremental ratio of baPWV with age. Conclusions This study is the first to show that SNP−617 affects the age-dependent increase in vascular stiffness. Our results indicate that low NRF2 activity induces premature vascular aging and could be targeted for the prevention of cardiovascular diseases associated with aging.
Purpose Pulse wave velocity (PWV), an indicator of vascular stiffness, increases with age and is increasingly recognized as an independent risk factor for cardiovascular disease (CVD). Although many mechanical and chemical factors underlie the stiffness of the elastic artery, genetic risk factors related to age-dependent increases in PWV in apparently healthy people are largely unknown. The transcription factor nuclear factor E2 (NF-E2)-related factor 2 (Nrf2), which is activated by unidirectional vascular pulsatile shear stress or oxidative stress, regulates vascular redox homeostasis. Previous reports have shown that a SNP in the NRF2 gene regulatory region (−617C>A; hereafter called SNP−617) affects NRF2 gene expression such that the minor A allele confers lower gene expression compared to the C allele, and it is associated with various diseases, including CVD. We aimed to investigate whether SNP−617 affects vascular stiffness with aging in apparently healthy people. Methods Analyzing wide-ranging data obtained from a public health survey performed in Japan, we evaluated whether SNP−617 affected brachial-ankle PWV (baPWV) in never-smoking healthy subjects (n = 642). We also evaluated the effects of SNP−617 on other cardiovascular and blood test measurements. Results We have shown that not only AA carriers (n = 55) but also CA carriers (n = 247) show arterial stiffness compared to CC carriers (n = 340). Furthermore, SNP−617 also affected blood pressure indexes such as systolic blood pressure and mean arterial pressure but not the ankle brachial pressure index, an indicator of atherosclerosis. Multivariate analysis showed that SNP−617 accelerates the incremental ratio of baPWV with age. Conclusions This study is the first to show that SNP−617 affects the age-dependent increase in vascular stiffness. Our results indicate that low NRF2 activity induces premature vascular aging and could be targeted for the prevention of cardiovascular diseases associated with aging.
PURPOSE:Pulse wave velocity (PWV), an indicator of vascular stiffness, increases with age and is increasingly recognized as an independent risk factor for cardiovascular disease (CVD). Although many mechanical and chemical factors underlie the stiffness of the elastic artery, genetic risk factors related to age-dependent increases in PWV in apparently healthy people are largely unknown. The transcription factor nuclear factor E2 (NF-E2)-related factor 2 (Nrf2), which is activated by unidirectional vascular pulsatile shear stress or oxidative stress, regulates vascular redox homeostasis. Previous reports have shown that a SNP in the NRF2 gene regulatory region (-617C>A; hereafter called SNP-617) affects NRF2 gene expression such that the minor A allele confers lower gene expression compared to the C allele, and it is associated with various diseases, including CVD. We aimed to investigate whether SNP-617 affects vascular stiffness with aging in apparently healthy people. METHODS:Analyzing wide-ranging data obtained from a public health survey performed in Japan, we evaluated whether SNP-617 affected brachial-ankle PWV (baPWV) in never-smoking healthy subjects (n = 642). We also evaluated the effects of SNP-617 on other cardiovascular and blood test measurements. RESULTS:We have shown that not only AA carriers (n = 55) but also CA carriers (n = 247) show arterial stiffness compared to CC carriers (n = 340). Furthermore, SNP-617 also affected blood pressure indexes such as systolic blood pressure and mean arterial pressure but not the ankle brachial pressure index, an indicator of atherosclerosis. Multivariate analysis showed that SNP-617 accelerates the incremental ratio of baPWV with age. CONCLUSIONS:This study is the first to show that SNP-617 affects the age-dependent increase in vascular stiffness. Our results indicate that low NRF2 activity induces premature vascular aging and could be targeted for the prevention of cardiovascular diseases associated with aging.
Audience Academic
Author Shimizu, Sunao
Shimizu, Eigo
Yamamoto, Masayuki
Kasai, Shuya
Suganuma, Hiroyuki
Itoh, Ken
Nakaji, Shigeyuki
Imoto, Seiya
Tsushima, Michiko
Yamazaki, Hiromi
Hasegawa, Takanori
Tomita, Hirofumi
Mimura, Junsei
Ushida, Yusuke
AuthorAffiliation 8 Department of Social Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
2 Department of Vegetable Life Science, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
4 Health Intelligence Center, The University of Tokyo, Minato-ku, Tokyo, Japan
Showa University School of Pharmacy, JAPAN
7 Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
6 Department of Cardiology and Nephrology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
5 Human Genome Center, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan
1 Department of Stress Response Science, Center for Advanced Medical Research, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
3 Department of Nature & Wellness Research, Innovation Division, Kagome Co., Ltd. Nasushiobara, Tochigi, Japan
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– notice: 2020 Shimizu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
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Current address: Department of Hematology-Oncology, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe, Kobe, Japan
Competing Interests: The authors have declared that no competing interests exist. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
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0000-0002-8183-4677
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Snippet Purpose Pulse wave velocity (PWV), an indicator of vascular stiffness, increases with age and is increasingly recognized as an independent risk factor for...
Pulse wave velocity (PWV), an indicator of vascular stiffness, increases with age and is increasingly recognized as an independent risk factor for...
PURPOSE:Pulse wave velocity (PWV), an indicator of vascular stiffness, increases with age and is increasingly recognized as an independent risk factor for...
Purpose Pulse wave velocity (PWV), an indicator of vascular stiffness, increases with age and is increasingly recognized as an independent risk factor for...
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SubjectTerms Age
Aging
Aging (Biology)
Alleles
Ankle
Arteriosclerosis
Atherosclerosis
Biology and Life Sciences
Biomedical research
Blood pressure
Cardiology
Cardiovascular disease
Cardiovascular diseases
Diabetes
Endothelium
Evaluation
Funding
Gene expression
Genetic aspects
Genomes
Health aspects
Health promotion
Health risks
Heart diseases
Homeostasis
Life sciences
Mechanical properties
Medical research
Medicine
Medicine and Health Sciences
Multivariate analysis
Nephrology
NRF2 protein
Nucleotides
Oxidative stress
Physical Sciences
Physiological aspects
Proteins
Public health
Research and Analysis Methods
Risk analysis
Risk factors
Senescence
Shear stress
Single nucleotide polymorphisms
Single-nucleotide polymorphism
Stiffness
Transcription factors
University graduates
Vascular resistance
Veins & arteries
Wave velocity
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Title Association of single nucleotide polymorphisms in the NRF2 promoter with vascular stiffness with aging
URI https://www.proquest.com/docview/2432836711
https://www.proquest.com/docview/2433238607
https://pubmed.ncbi.nlm.nih.gov/PMC7418968
https://doaj.org/article/392cf8f5ae28473ab08d93475b583575
http://dx.doi.org/10.1371/journal.pone.0236834
Volume 15
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