Bacillus Calmette-Guérin and TLR4 agonist prevent cardiovascular hypertrophy and fibrosis by regulating immune microenvironment
| Autor: | Jun Yan, Wen Jin, Yuying Liu, Wenfeng Cai, Fang Hua, Hong-Zhen Yang, Bing Mu Xin, Bin Yuan, Han Zhi Liu, Zhi Rong Chen, Bing Cui, Huimin Yan, Zhuowei Hu |
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| Rok vydání: | 2008 |
| Předmět: |
Agonist
Lipopolysaccharides Male medicine.medical_specialty medicine.drug_class Cardiac fibrosis Immunology Cardiomegaly Mice Inbred Strains Cardiovascular System Muscle hypertrophy Glycogen Synthase Kinase 3 Interferon-gamma Mice Immune system Th2 Cells Fibrosis Transforming Growth Factor beta Internal medicine medicine Immunology and Allergy Animals Rats Wistar Mitogen-Activated Protein Kinase Kinases Glycogen Synthase Kinase 3 beta business.industry Escherichia coli Proteins Myocardium Dendritic Cells Th1 Cells medicine.disease Toll-Like Receptor 2 Rats Toll-Like Receptor 4 TLR2 Disease Models Animal Endocrinology Heart failure TLR4 BCG Vaccine lipids (amino acids peptides and proteins) business Proto-Oncogene Proteins c-akt Acyltransferases |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 180(11) |
| ISSN: | 0022-1767 |
| Popis: | Hypertension-induced cardiovascular hypertrophy and fibrosis are critical in the development of heart failure. The activity of TLRs has been found to be involved in the development of pressure overload-induced myocardial hypertrophy and cardiac fibrosis. We wondered whether vaccine bacillus Calmette-Guérin (BCG), which activated TLR4 to elicit immune responses, modulated the pressure overload-stimulated cardiovascular hypertrophy and cardiac fibrosis in the murine models of abdominal aortic constriction (AAC)-induced hypertension. Before or after AAC, animals received BCG, TLR4 agonist, IFN-γ, or TLR4 antagonist i.p. BCG and TLR4 agonist significantly prevented AAC-induced cardiovascular hypertrophy and reactive cardiac fibrosis with no changes in hemodynamics. Moreover, TLR4 antagonist reversed the BCG- and TLR4 agonist-induced actions of anti-cardiovascular hypertrophy and cardiac fibrosis. BCG decreased the expression of TLR2 or TLR4 on the heart tissue but TLR4 agonist increased the expression of TLR2 or TLR4 on the immune cells that infiltrate into the heart tissue. This led to an increased expression ratio of IFN-γ/TGF-β in the heart. The cardiac protective effects of BCG and TLR4 agonist are related to their regulation of ERK-Akt and p38-NF-κB signal pathways in the heart. In conclusion, the activity of TLR4 plays a critical role in the mediation of pressure overload-induced myocardial hypertrophy and fibrosis. The regulation of immune responses by BCG and TLR4 agonist has a great potential for the prevention and treatment of hypertension-induced myocardial hypertrophy and cardiac fibrosis. |
| Databáze: | OpenAIRE |
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