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Dual Activation of TRIF and MyD88 Adaptor Proteins by Angiotensin II Evokes Opposing Effects on Pressure, Cardiac Hypertrophy, and Inflammatory Gene Expression
- Source :
- Hypertension (Dallas, Tex. : 1979). 66(3)
- Publication Year :
- 2015
-
Abstract
- Hypertension is recognized as an immune disorder whereby immune cells play a defining role in the genesis and progression of the disease. The innate immune system and its component toll-like receptors are key determinants of the immunologic outcome through their proinflammatory response. Toll-like receptor–activated signaling pathways use several adaptor proteins of which adaptor proteins myeloid differentiation protein 88 (MyD88) and toll-interleukin receptor domain–containing adaptor protein–inducing interferon-β (TRIF) define 2 major inflammatory pathways. In this study, we compared the contributions of MyD88 and TRIF adaptor proteins to angiotensin II (Ang II)–induced hypertension and cardiac hypertrophy in mice. Deletion of MyD88 did not prevent cardiac hypertrophy and the pressor response to Ang II tended to increase. Moreover, the increase in inflammatory gene expression ( Tnfa, Nox4 , and Agtr1a ) was significantly greater in the heart and kidney of MyD88-deficient mice when compared with wild-type mice. Thus, pathways involving MyD88 may actually restrain the inflammatory responses. However, in mice with nonfunctional TRIF ( Trif mut mice), Ang II–induced hypertension and cardiac hypertrophy were abrogated, and proinflammatory gene expression in heart and kidneys was unchanged or decreased. Our results indicate that Ang II induces activation of a proinflammatory innate immune response, causing hypertension and cardiac hypertrophy. These effects require functional adaptor protein TRIF-mediated pathways. However, the common MyD88-dependent signaling pathway, which is also activated simultaneously by Ang II, paradoxically exerts a negative regulatory influence on these responses.
- Subjects :
- medicine.medical_specialty
Gene Expression
Blood Pressure
Cardiomegaly
Biology
Article
Proinflammatory cytokine
Mice
Internal medicine
Internal Medicine
medicine
Animals
Inflammation
Mice, Knockout
Angiotensin II
Signal transducing adaptor protein
medicine.disease
Adaptor Proteins, Vesicular Transport
Endocrinology
TRIF
Myeloid Differentiation Factor 88
Tumor necrosis factor alpha
Immune disorder
Signal transduction
Subjects
Details
- ISSN :
- 15244563
- Volume :
- 66
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Hypertension (Dallas, Tex. : 1979)
- Accession number :
- edsair.doi.dedup.....cfcd324fd17e38eb00e7ac57649b240f