Cell death & disease, 2020-02, Vol.11 (2), p.131, Article 131
2020
Details
- Autor(en) / Beteiligte
- Titel
- A novel STAT3 inhibitor attenuates angiotensin II-induced abdominal aortic aneurysm progression in mice through modulating vascular inflammation and autophagy
- Ist Teil von
- Cell death & disease, 2020-02, Vol.11 (2), p.131, Article 131
- Ort / Verlag
- England: Springer Nature B.V
- Erscheinungsjahr
- 2020
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Abdominal Aortic aneurysm (AAA) is associated with chronic inflammation, cells apoptosis, and impairment of autophagy. BP-1-102, a novel potent STAT3 inhibitor, has been recently reported to significantly block inflammation-related signaling pathways of JAK2/STAT3 and NF-κB, as well as regulate autophagy. However, its role in vascular inflammation and AAA progression remains to be elucidated. In the present study, the effect and potential mechanisms of BP-1-102 on angiotensin II (AngII) induced AAA in ApoE mice were investigated. AAA was induced in ApoE mice with infusion of AngII for 28 days. BP-1-102 was administrated orally to mice every other day. Mice were sacrificed on day 7, day 14, and day 28 to evaluate the treatment effects. BP-1-102 markedly decreased AAA incidence and aortic diameter, maintained elastin structure and volume, reduced the expression of pro-inflammatory cytokines and MMPs, and inhibited inflammatory cells infiltration. Moreover, BP-1-102 dramatically reduced the expression of JAK2, p-STAT3, p-NF-κB, and Bcl-xL but maintained the expression of LC3B and Beclin in AAA tissues. In vitro, vascular smooth muscle cells (VSMCs) were treated with AngII and/or BP-1-102 at indicated time and concentration. BP-1-102 inhibited AngII-induced JAK2/STAT3 and NF-κB signaling activation and maintained autophagy-related proteins expression in VSMCs. Taken together, our findings suggest that BP-1-102 inhibits vascular inflammation and AAA progression through decreasing JAK2/STAT3 and NF-κB activation and maintaining autophagy.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-4889eISSN: 2041-4889DOI: 10.1038/s41419-020-2326-2Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7028955
- Format
- –
- Schlagworte
- Aminosalicylic Acids - pharmacology, Aneurysms, Angiotensin, Angiotensin II, Animals, Aorta, Aorta, Abdominal - drug effects, Aorta, Abdominal - metabolism, Aorta, Abdominal - pathology, Aortic Aneurysm, Abdominal - chemically induced, Aortic Aneurysm, Abdominal - metabolism, Aortic Aneurysm, Abdominal - pathology, Aortic Aneurysm, Abdominal - prevention & control, Aortic aneurysms, Aortitis - chemically induced, Aortitis - metabolism, Aortitis - pathology, Aortitis - prevention & control, Apolipoprotein E, Apoptosis, Apoptosis - drug effects, Autophagy, Autophagy - drug effects, Autophagy-Related Proteins - metabolism, Bcl-x protein, Cells, Cultured, Cytokines, Disease Models, Animal, Elastin, Inflammation, Janus kinase 2, Janus Kinase 2 - metabolism, Male, Mice, Knockout, ApoE, NF-kappa B - metabolism, NF-κB protein, Oral administration, Phagocytosis, Phosphorylation, Signal Transduction, Smooth muscle, Stat3 protein, STAT3 Transcription Factor - antagonists & inhibitors, STAT3 Transcription Factor - metabolism, Sulfonamides - pharmacology, Vascular Remodeling - drug effects