ORCID Profile
0000-0002-3973-340X
Current Organisation
Vanderbilt University Medical Center
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Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2011
DOI: 10.1161/ATVBAHA.111.227629
Abstract: Interleukin 17A (IL17A) is involved in many inflammatory processes, but its role in atherosclerosis remains controversial. We examined the role of IL17A in mouse and human atherosclerosis. Atherosclerosis was induced in apolipoprotein E (ApoE) −/− and IL17A/ApoE −/− mice using high-fat feeding, angiotensin II infusion, or partial carotid ligation. In ApoE −/− mice, 3 months of high-fat diet induced interferon-γ production by splenic lymphocytes, and this was abrogated in IL17A/ApoE −/− mice. IL17A/ApoE −/− mice had reduced aortic superoxide production, increased aortic nitric oxide levels, decreased aortic leukocyte and dendritic cell infiltration, and reduced weight gain after a high-fat diet compared with ApoE −/− mice. Despite these favorable effects, IL17A deficiency did not affect aortic plaque burden after a high-fat diet or angiotensin II infusion. In a partial carotid ligation model, IL17A deficiency did not affect percentage of stenosis but reduced outward remodeling. In this model, neutralization of the related isoform, IL17F, in IL17A/ApoE −/− mice did not alter atherosclerosis. Finally, there was no correlation between IL17A levels and carotid intima-media thickness in humans. IL17 contributes to vascular and systemic inflammation in experimental atherosclerosis but does not alter plaque burden. The changes in plaque composition caused by IL17 might modulate plaque stability.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 14-12-2010
DOI: 10.1161/CIRCULATIONAHA.109.930446
Abstract: The pathogenesis of hypertension remains poorly understood, and treatment is often unsuccessful. Recent evidence suggests that the adaptive immune response plays an important role in this disease. Various hypertensive stimuli cause T-cell activation and infiltration into target organs such as the vessel and the kidney, which promotes vascular dysfunction and blood pressure elevation. Classically, T-cell activation requires T-cell receptor ligation and costimulation. The latter often involves interaction between B7 ligands (CD80 and CD86) on antigen-presenting cells with the T-cell coreceptor CD28. This study was therefore performed to examine the role of this pathway in hypertension. Angiotensin II–induced hypertension increased the presence of activated (CD86 + ) dendritic cells in secondary lymphatic tissues. Blockade of B7-dependent costimulation with CTLA4-Ig reduced both angiotensin II– and deoxycorticosterone acetate (DOCA)–salt–induced hypertension. Activation of circulating T cells, T-cell cytokine production, and vascular T-cell accumulation caused by these hypertensive stimuli were abrogated by CTLA4-Ig. Furthermore, in mice lacking B7 ligands, angiotensin II caused minimal blood pressure elevation and vascular inflammation, and these effects were restored by transplantation with wild-type bone marrow. T-cell costimulation via B7 ligands is essential for development of experimental hypertension, and inhibition of this process could have therapeutic benefit in the treatment of this disease.
Publisher: American Society for Clinical Investigation
Date: 17-09-2014
DOI: 10.1172/JCI74084
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 15-04-2016
DOI: 10.1161/CIRCRESAHA.115.308111
Abstract: Accumulating evidence supports a role of adaptive immunity and particularly T cells in the pathogenesis of hypertension. Formation of memory T cells, which requires the costimulatory molecule CD70 on antigen-presenting cells, is a cardinal feature of adaptive immunity. To test the hypothesis that CD70 and immunologic memory contribute to the blood pressure elevation and renal dysfunction mediated by repeated hypertensive challenges. We imposed repeated hypertensive challenges using either N ω -nitro-L-arginine methyl ester hydrochloride (L-NAME)/high salt or repeated angiotensin II stimulation in mice. During these challenges effector memory T cells (T EM ) accumulated in the kidney and bone marrow. In the L-NAME/high-salt model, memory T cells of the kidney were predominant sources of interferon-γ and interleukin-17A, known to contribute to hypertension. L-NAME/high salt increased macrophage and dendritic cell surface expression of CD70 by 3- to 5-fold. Mice lacking CD70 did not accumulate T EM cells and did not develop hypertension to either high salt or the second angiotensin II challenge and were protected against renal damage. Bone marrow–residing T EM cells proliferated and redistributed to the kidney in response to repeated salt feeding. Adoptively transferred T EM cells from hypertensive mice homed to the bone marrow and spleen and expanded on salt feeding of the recipient mice. Our findings illustrate a previously undefined role of CD70 and long-lived T EM cells in the development of blood pressure elevation and end-organ damage that occur on delayed exposure to mild hypertensive stimuli. Interventions to prevent repeated hypertensive surges could attenuate formation of hypertension-specific T EM cells.
Location: United States of America
No related grants have been discovered for Wei Chen.