The DOI matches its Crossref record; 18 of the 18 references it cites were found in a registry or an index.
Blockade of the Nuclear Factor-κB Pathway in the Endothelium Prevents Insulin Resistance and Prolongs Life Spans
Open accessAbstract
Background—: Nuclear factor-κB (NF-κB) signaling plays critical roles in physiological and pathological processes such as responses to inflammation and oxidative stress. Methods and Results—: To examine the role of endothelial NF-κB signaling in vivo, we generated transgenic mice expressing dominant-negative IκB under the Tie2 promoter/enhancer (E-DNIκB mice). These mice exhibited functional inhibition of NF-κB signaling specifically in endothelial cells. Although E-DNIκB mice displayed no overt phenotypic changes when young and lean, they were protected from the development of insulin resistance associated with obesity, whether diet- or genetics-induced. Obesity-induced macrophage infiltration into adipose tissue and plasma oxidative stress markers were decreased and blood flow and mitochondrial content in muscle and active-phase locomotor activity were increased in E-DNIκB mice. In addition to inhibition of obesity-related metabolic deteriorations, blockade of endothelial NF-κB signaling prevented age-related insulin resistance and vascular senescence and, notably, prolonged life span. These antiaging phenotypes were also associated with decreased oxidative stress markers, increased muscle blood flow, enhanced active-phase locomotor activity, and aortic upregulation of mitochondrial sirtuin-related proteins. Conclusions—: The endothelium plays important roles in obesity- and age-related disorders through intracellular NF-κB signaling, thereby ultimately affecting life span. Endothelial NF-κB signaling is a potential target for treating the metabolic syndrome and for antiaging strategies.
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Cites
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Cited by
Ungvari, Z., Tarantini, S., Donato, A. J., Galvan, V., & Csiszar, A. (2018) · Circulation Research · doi:10.1161/circresaha.118.311378 · Cited by 919
Mechanisms of Dysfunction in the Aging Vasculature and Role in Age-Related Disease
Donato, A. J., Machin, D. R., & Lesniewski, L. A. (2018) · Circulation Research · doi:10.1161/circresaha.118.312563 · Cited by 688
The Aging Cardiovascular System
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Metadata
- Authors
- Hasegawa, Y., Saito, T., Ogihara, T., Ishigaki, Y., Yamada, T., Imai, J., Uno, K., Gao, J., Kaneko, K., Shimosawa, T., Asano, T., Fujita, T., Oka, Y., & Katagiri, H.
- Venue
- Circulation
- Published
- 2012-03-06
- Volume
- 125
- Issue
- 9
- Pages
- 1122-1133
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2168182860
- Cited by
- 169
- References
- 18
- FWCI
- 10.34
- Type
- journal article
- Language
- en
- Open access
- bronze
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- CoChat. (2026). Citation check: Blockade of the Nuclear Factor-κB Pathway in the Endothelium Prevents Insulin Resistance and Prolongs Life Spans. https://app.cochat.ai/papers/10.1161/circulationaha.111.054346
- The paper
- Hasegawa, Y., Saito, T., Ogihara, T., Ishigaki, Y., Yamada, T., Imai, J., Uno, K., Gao, J., Kaneko, K., Shimosawa, T., Asano, T., Fujita, T., Oka, Y., & Katagiri, H. (2012). Blockade of the Nuclear Factor-κB Pathway in the Endothelium Prevents Insulin Resistance and Prolongs Life Spans. Circulation. https://doi.org/10.1161/circulationaha.111.054346
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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