The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
DC isoketal-modified proteins activate T cells and promote hypertension
Open accessAbstract
Oxidative damage and inflammation are both implicated in the genesis of hypertension; however, the mechanisms by which these stimuli promote hypertension are not fully understood. Here, we have described a pathway in which hypertensive stimuli promote dendritic cell (DC) activation of T cells, ultimately leading to hypertension. Using multiple murine models of hypertension, we determined that proteins oxidatively modified by highly reactive γ-ketoaldehydes (isoketals) are formed in hypertension and accumulate in DCs. Isoketal accumulation was associated with DC production of IL-6, IL-1β, and IL-23 and an increase in costimulatory proteins CD80 and CD86. These activated DCs promoted T cell, particularly CD8+ T cell, proliferation; production of IFN-γ and IL-17A; and hypertension. Moreover, isoketal scavengers prevented these hypertension-associated events. Plasma F2-isoprostanes, which are formed in concert with isoketals, were found to be elevated in humans with treated hypertension and were markedly elevated in patients with resistant hypertension. Isoketal-modified proteins were also markedly elevated in circulating monocytes and DCs from humans with hypertension. Our data reveal that hypertension activates DCs, in large part by promoting the formation of isoketals, and suggest that reducing isoketals has potential as a treatment strategy for this disease.
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Cites
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Role of the T cell in the genesis of angiotensin II–induced hypertension and vascular dysfunction
Guzik, T. J., Hoch, N. E., Brown, K. A., McCann, L. A., Rahman, A., Dikalov, S., Goronzy, J., Weyand, C., & Harrison, D. G. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070657 · Cited by 1,736
Self-citationLandmesser, U., Dikalov, S., Price, S. R., McCann, L., Fukai, T., Holland, S. M., Mitch, W. E., & Harrison, D. G. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200314172 · Cited by 1,660
Self-citationDiscovering motifs in ranked lists of DNA sequences
Eden, E., Lipson, D., Yogev, S., & Yakhini, Z. (2007) · PLoS Computational Biology · doi:10.1371/journal.pcbi.0030039 · Cited by 696
Nox1 Is Involved in Angiotensin II–Mediated Hypertension: A Study in Nox1-Deficient Mice
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Clinical Relevance of Biomarkers of Oxidative Stress
Frijhoff, J., Winyard, P. G., Zarkovic, N., Davies, S. S., Stocker, R., Cheng, D., Knight, A. R., Taylor, E. L., Oettrich, J., Ruskovska, T., et al. (2015) · Antioxidants & Redox Signaling · doi:10.1089/ars.2015.6317 · Cited by 909
Self-citationInflammation, Immunity, and Hypertensive End-Organ Damage
McMaster, W. G., Kirabo, A., Madhur, M. S., & Harrison, D. G. (2015) · Circulation Research · doi:10.1161/circresaha.116.303697 · Cited by 708
Self-citationVascular Inflammation and Oxidative Stress: Major Triggers for Cardiovascular Disease
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Oxidative Stress and Hypertension
Griendling, K. K., Camargo, L. L., Rios, F. J., Alves-Lopes, R., Montezano, A. C., & Touyz, R. M. (2021) · Circulation Research · doi:10.1161/circresaha.121.318063 · Cited by 573
Metadata
- Authors
- Kirabo, A., Fontana, V., de Faria, A. P. C., Loperena, R., Galindo, C. L., Wu, J., Bikineyeva, A. T., Dikalov, S., Xiao, L., Chen, W., Saleh, M. A., Trott, D. W., Itani, H. A., Vinh, A., Amarnath, V., Amarnath, K., Guzik, T. J., Bernstein, K. E., Shen, X. Z., Shyr, Y., Chen, S.-C., Mernaugh, R. L., Laffer, C. L., Elijovich, F., Davies, S. S., Moreno, H., Madhur, M. S., Roberts, J., & Harrison, D. G.
- Venue
- Journal of Clinical Investigation
- Published
- 2014-09-17
- Volume
- 124
- Issue
- 10
- Pages
- 4642-4656
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W1968908220
- Cited by
- 538
- References
- 6
- FWCI
- 14.52
- Type
- journal article
- Language
- en
- Open access
- green
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- Kirabo, A., Fontana, V., de Faria, A. P. C., Loperena, R., Galindo, C. L., Wu, J., Bikineyeva, A. T., Dikalov, S., Xiao, L., Chen, W., Saleh, M. A., Trott, D. W., Itani, H. A., Vinh, A., Amarnath, V., Amarnath, K., Guzik, T. J., Bernstein, K. E., Shen, X. Z., . . . Harrison, D. G. (2014). DC isoketal-modified proteins activate T cells and promote hypertension. Journal of Clinical Investigation. https://doi.org/10.1172/jci74084
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