Browning of perivascular adipose tissue protects against thoracic aortic aneurysm
血管周围脂肪组织褐变可预防胸主动脉瘤
基本信息
- 批准号:10580855
- 负责人:
- 金额:$ 58.62万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-04-01 至 2026-03-31
- 项目状态:未结题
- 来源:
- 关键词:AccelerationAddressAdipocytesAdipose tissueAffectAneurysmAortaAortic AneurysmApoptosisAtherosclerosisBlood VesselsBrown FatCardiacCardiovascular DiseasesCharacteristicsChestClinicalClinical TreatmentClinical TrialsCoculture TechniquesConditioned Culture MediaDataDevelopmentDiseaseDissectionFatty AcidsFatty acid glycerol estersFunctional disorderGenerationsGenesGenetic Predisposition to DiseaseHealthHeritabilityHomeostasisHumanHypertensionIn VitroInduction of ApoptosisInflammationInflammatoryInfusion proceduresKnockout MiceKnowledgeLesionLifeMediatingMetabolic DiseasesModelingMorbidity - disease rateMusNitrogen DioxideOperative Surgical ProceduresOther GeneticsOutcomeOxidative StressPathologyPatientsPharmaceutical PreparationsPharmacotherapyPhase II Clinical TrialsProcessPropertyProteinsRepressionResearchRisk AdjustmentRoleRuptureSignal TransductionSmooth Muscle MyocytesTestingThoracic Aortic AneurysmTransgenic MiceVascular DiseasesVascular Smooth MuscleWorkadipokinesclinical translationepidemiology studygain of functiongenetic approachin vivoinflammatory markerknock-downloss of functionmortalitynitrated conjugated linoleic acidnovelnovel drug classnovel therapeutic interventionoverexpressionparacrineperioperative mortalitypharmacologicpreventprogramsrepairedresistin
项目摘要
PROJECT SUMMARY/ABSTRACT
Thoracic aortic aneurysm (TAA) is a life-threatening disease and has a high mortality rate if rupture occurs.
Currently, apart from endovascular or open surgery repair, no drug has been demonstrated to be effective for
TAA treatment. Even though some patients with TAA have evidence of a heritable aortopathy, about 75% of
TAA patients have severe aortic damage without a clear genetic etiology. The scant mechanistic knowledge is
limiting the development of medications for the treatment of TAA, thus highlighting a pressing need for better
understanding TAA formation and progression. Aorta is naturally surrounded by perivascular adipose tissue
(PVAT). Recent large-scale epidemiological studies demonstrated that PVAT was highly associated with a
significantly higher adjusted risk of all-cause cardiac mortality. We and others documented that brown-like
PVAT contributes to vascular homeostasis in health, while whitening of PVAT is dysfunctional and contributes
to development of the vascular diseases. A causal relationship between PVAT and TAA and the underlying
mechanisms remain unknown. Our preliminary studies indicate that the PVAT near the TAA lesion in patients
lost brown characteristics, and that TAA formation was dramatically increased in mice that lack normal PVAT,
suggesting that dysfunctional PVAT is associated with TAA. The conditioned medium from PVAT of TAA
patients induced apoptosis and inflammation in human aortic smooth muscle cells, suggesting that signaling
from PVAT can cause loss of vascular smooth muscle cells (VSMC) in the aorta, which may promote TAA
lesion. It is unknown whether browning of PVAT could protect against TAA. PR-domain containing 16
(PRDM16) is a determinant of browning gene programs. We show that PRDM16 expression in PVAT of TAA
patients is significantly reduced when compared to that in normal PVAT. PRDM16 inhibited resistin expression
in PVAT. We found that nitrated conjugated linoleic acid (NO2-CLA) induced the browning of human PVAT
adipocytes by mediating PRDM16 signaling. Based on these data, we hypothesize that PRDM16-mediated
PVAT browning prevents TAA formation. We will determine that 1) PRDM16 in PVAT prevents and reverses
TAA in mice; 2) PRDM16 inhibits TAA by regulating PVAT crosstalk with VSMC; 3) NO2-CLA prevents TAA by
targeting PRDM16. Outcomes will demonstrate that a previously unrecognized process involving loss of
browning features in PVAT promotes TAA formation through crosstalk to VSMC. This work will accelerate
clinical translation of a nitro-fatty acid-based treatment for TAA targeting PVAT homeostasis with this new
class of drugs, currently on clinical trials for other diseases.
项目总结/文摘
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
YUQING Eugene CHEN其他文献
YUQING Eugene CHEN的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('YUQING Eugene CHEN', 18)}}的其他基金
Browning of perivascular adipose tissue protects against thoracic aortic aneurysm
血管周围脂肪组织褐变可预防胸主动脉瘤
- 批准号:
10462357 - 财政年份:2022
- 资助金额:
$ 58.62万 - 项目类别:
Development of gene editing based therapy for cardiovascular diseases
开发基于基因编辑的心血管疾病疗法
- 批准号:
10652321 - 财政年份:2021
- 资助金额:
$ 58.62万 - 项目类别:
Development of gene editing based therapy for cardiovascular diseases
开发基于基因编辑的心血管疾病疗法
- 批准号:
10313701 - 财政年份:2021
- 资助金额:
$ 58.62万 - 项目类别:
Development of gene editing based therapy for cardiovascular diseases
开发基于基因编辑的心血管疾病疗法
- 批准号:
10441548 - 财政年份:2021
- 资助金额:
$ 58.62万 - 项目类别:
IDOL and dyslipidemia in cardiovascular diseases
IDOL 与心血管疾病中的血脂异常
- 批准号:
10221773 - 财政年份:2019
- 资助金额:
$ 58.62万 - 项目类别:
IDOL and dyslipidemia in cardiovascular diseases
IDOL 与心血管疾病中的血脂异常
- 批准号:
10451711 - 财政年份:2019
- 资助金额:
$ 58.62万 - 项目类别:
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 58.62万 - 项目类别:
Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 58.62万 - 项目类别:
Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 58.62万 - 项目类别:
Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 58.62万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 58.62万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 58.62万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 58.62万 - 项目类别:
EU-Funded
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 58.62万 - 项目类别:
Standard Grant
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 58.62万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 58.62万 - 项目类别:
Research Grant














{{item.name}}会员




