Open AccessPharmacological inhibition of STAT3 by BP‐1‐102 inhibits intracranial aneurysm formation and rupture in mice through modulating inflammatory response
Author(s) -
Jiang Zhixian,
Huang Jiaxin,
You Lingtong,
Zhang Jinning,
Li Bingyu
Publication year - 2021
Publication title -
pharmacology research and perspectives
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.975
H-Index - 27
ISSN - 2052-1707
DOI - 10.1002/prp2.704
Subject(s) - vascular smooth muscle , mmp9 , matrix metalloproteinase , inflammation , western blot , mmp2 , electrical impedance myography , stat3 , elastin , medicine , signal transduction , nf κb , elastase , aneurysm , chemistry , pharmacology , cancer research , downregulation and upregulation , endocrinology , pathology , biology , microbiology and biotechnology , smooth muscle , enzyme , biochemistry , surgery , gene , vasodilation
As an inhibitor of STAT3, BP‐1‐102 can regulate the inflammation response caused by vascular smooth muscle cells (VSMCs) by inhibiting the JAK/STAT3/NF‐κB pathway, thereby attenuating the symptoms of intracranial aneurysm (IA). IA mouse model was established by stereotactic injection of elastase to evaluate the effect of BP‐1‐102. The expression levels of smooth muscle markers and matrix metalloproteinases (MMPs) were detected by qRT‐PCR, and the levels of inflammatory factors were detected by ELISA and qRT‐PCR. The protein levels of the NF‐κB signaling pathway factors were examined by Western blot. BP‐1‐102 reduced blood pressure in aneurysm mice, up‐regulated smooth muscle cell markers MHC, SMA, and SM22, and down‐regulated the expression of MMP2 and MMP9 in vascular tissues. At the same time, BP‐1‐102 also down‐regulated the expression levels of inflammatory response factors and the NF‐κB pathway proteins. In the IA model, BP‐1‐102 can reduce the expression of inflammatory factors and MMPs bound to NF‐κB by inhibiting the activation of the JAK/STAT3/NF‐κB pathway proteins, and then restore the vascular wall elastin to reduce blood pressure, thereby treating aneurysm.