The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.
Interleukin-6 Overexpression Induces Pulmonary Hypertension
Open accessAbstract
Inflammatory cytokine interleukin (IL)-6 is elevated in the serum and lungs of patients with pulmonary artery hypertension (PAH). Several animal models of PAH cite the potential role of inflammatory mediators. We investigated role of IL-6 in the pathogenesis of pulmonary vascular disease. Indices of pulmonary vascular remodeling were measured in lung-specific IL-6–overexpressing transgenic mice (Tg + ) and compared to wild-type (Tg − ) controls in both normoxic and chronic hypoxic conditions. The Tg + mice exhibited elevated right ventricular systolic pressures and right ventricular hypertrophy with corresponding pulmonary vasculopathic changes, all of which were exacerbated by chronic hypoxia. IL-6 overexpression increased muscularization of the proximal arterial tree, and hypoxia enhanced this effect. It also reproduced the muscularization and proliferative arteriopathy seen in the distal arteriolar vessels of PAH patients. The latter was characterized by the formation of occlusive neointimal angioproliferative lesions that worsened with hypoxia and were composed of endothelial cells and T-lymphocytes. IL-6–induced arteriopathic changes were accompanied by activation of proangiogenic factor, vascular endothelial growth factor, the proproliferative kinase extracellular signal-regulated kinase, proproliferative transcription factors c-MYC and MAX, and the antiapoptotic proteins survivin and Bcl-2 and downregulation of the growth inhibitor transforming growth factor-β and proapoptotic kinases JNK and p38. These findings suggest that IL-6 promotes the development and progression of pulmonary vascular remodeling and PAH through proproliferative antiapoptotic mechanisms.
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Cited by
IL-6 as a keystone cytokine in health and disease
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Inflammation and immunity in the pathogenesis of pulmonary arterial hypertension
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Mechanisms of disease: pulmonary arterial hypertension
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Metadata
- Authors
- Steiner, M. K., Syrkina, O. L., Kolliputi, N., Mark, E. J., Hales, C. A., & Waxman, A. B.
- Venue
- Circulation Research
- Published
- 2009-01-30
- Volume
- 104
- Issue
- 2
- Pages
- 236-244
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W2145237733
- Cited by
- 655
- References
- 50
- FWCI
- 23.37
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Steiner, M. K., Syrkina, O. L., Kolliputi, N., Mark, E. J., Hales, C. A., & Waxman, A. B. (2009). Interleukin-6 Overexpression Induces Pulmonary Hypertension. Circulation Research. https://doi.org/10.1161/circresaha.108.182014
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