Anti-high mobility group box-1 antibody attenuated vascular smooth muscle cell phenotypic switching and vascular remodelling after subarachnoid haemorrhage in rats

Autor: Luodan Liang, Liang Wang, Yue Wu, Zhaosi Zhang, Xiaochuan Sun, Jianjun Zhong
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
medicine.medical_specialty
Vascular smooth muscle
Perforation (oil well)
Phenotypic switching
Myocytes
Smooth Muscle
chemical and pharmacologic phenomena
Brain Edema
Vascular Remodeling
HMGB1
Muscle
Smooth
Vascular
Vascular remodelling in the embryo
Rats
Sprague-Dawley
03 medical and health sciences
Phosphatidylinositol 3-Kinases
0302 clinical medicine
Internal medicine
medicine
Animals
cardiovascular diseases
Osteopontin
HMGB1 Protein
Cells
Cultured
Angiotensin II receptor type 1
biology
Chemistry
General Neuroscience
Antibodies
Monoclonal
Subarachnoid Hemorrhage
030104 developmental biology
Endocrinology
Phenotype
Vasoconstriction
Basilar Artery
biology.protein
Microglia
medicine.symptom
Proto-Oncogene Proteins c-akt
030217 neurology & neurosurgery
Signal Transduction
Zdroj: Neuroscience letters. 708
ISSN: 1872-7972
Popis: Although cerebral vascular smooth muscle cell (VSMC) phenotypic switching is involved in the vascular dysfunction after subarachnoid haemorrhage (SAH), the precise mechanisms are still unclear. High mobility group box-1 (HMGB1) has been identified as a modulator in VSMC proliferation. The purpose of this study was to investigate the potential role of HMGB1 in the VSMC phenotypic switching following SAH. An endovascular perforation SAH model was used in our experiments. The expression levels of HMGB1, α-smooth muscle actin (α-SMA), osteopontin (OPN), smooth muscle myosin heavy chain (SM-MHC), embryonic smooth muscle myosin heavy chain (Smemb), TXA2, PAR-1 and AT1 receptor were evaluated by Western blot analyses. Iba1-positive cells and apoptotic cells were determined by immunofluorescence staining and TUNEL staining, respectively. Vasoconstriction of the isolated basilar artery was stimulated by thrombin and KCl. We found that HMGB1 expression was markedly increased following SAH, and anti-HMGB1 mAb significantly reversed VSMC phenotypic switching and vascular remodelling in rats. However, the effects of HMGB1 on VSMC phenotypic switching were partly blocked in the presence of SC79, a potent activator of phosphatidylinositol-3-kinase-AKT (PI3K/AKT). Furthermore, the enhanced vasoconstriction and decreased cerebral cortical blood flow induced by SAH were reversed by anti-HMGB1 mAb. Finally, we found that anti-HMGB1 mAb attenuated microglial activation and brain oedema, ameliorating neurological dysfunction. These results indicated that HMGB1 is a useful regulator of VSMC phenotypic switching and vascular remodelling following SAH and might be exploited as a novel therapeutic target for delayed cerebral ischaemia.
Databáze: OpenAIRE
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