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Anti-Diabetic Atherosclerosis by Inhibiting High Glucose-Induced Vascular Smooth Muscle Cell Proliferation via Pin1/BRD4 Pathway
- Source :
- Oxidative Medicine and Cellular Longevity, Oxidative Medicine and Cellular Longevity, Vol 2020 (2020)
- Publication Year :
- 2020
- Publisher :
- Hindawi, 2020.
-
Abstract
- Background and purpose. Vascular smooth muscle cells (VSMC) proliferation and migration is the important pathological process of diabetic atherosclerosis. Bromine domain protein 4 (BRD4) is involved in cell proliferation and inflammatory disease. Pin1 enhances BRD4 stability and its transcriptional activity. This study aimed to explore the possible mechanism of Pin1/BRD4 in diabetic atherosclerosis. Methods. Diabetic Apoe-/- mice induced by streptozotocin were treated with vehicle, the Pin1 inhibitor juglone, or the BRD4 inhibitor JQ1 for 3 weeks. VSMCs were pretreated with juglone, JQ1, or vehicle for 45 min, and then exposed to high glucose for 48 h. Hematoxylin–eosin staining was performed to assess atherosclerotic plaques of the thoracic aorta. Western blotting was used to detect expression levels of Pin1, BRD4, cyclin D1, and matrix metalloproteinase-9 (MMP-9) in the thoracic aorta and VSMCs. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and transwell assay were used to measure proliferation and migration of VSMCs. Results. Juglone and JQ1 significantly improved atherosclerosis of diabetic Apoe-/- mice and reduced high glucose-induced VSMC proliferation and migration. Cyclin D1 and MMP-9 levels in the thoracic aorta were lower in diabetic Apoe-/- mice treated with juglone and JQ1 compared with vehicle-treated diabetic Apoe-/- mice. Additionally, BRD4 protein expression in high glucose-induced VSMCs was inhibited by juglone and JQ1. Upregulation of Pin1 expression by transduction of the Pin1 plasmid vector promoted BRD4 expression induced by high glucose, and stimulated proliferation and migration of VSMCs. Conclusions. Inhibition of Pin1/BRD4 pathway may improve diabetic atherosclerosis by inhibiting proliferation and migration of VSMCs.
- Subjects :
- 0301 basic medicine
Male
Aging
Vascular smooth muscle
Article Subject
030204 cardiovascular system & hematology
Pharmacology
Biochemistry
Muscle, Smooth, Vascular
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
Cyclin D1
Downregulation and upregulation
medicine.artery
medicine
Thoracic aorta
Animals
Humans
Cell Proliferation
QH573-671
Cell growth
Nuclear Proteins
Cell Biology
General Medicine
Streptozotocin
Atherosclerosis
Blot
030104 developmental biology
Glucose
chemistry
cardiovascular system
Cytology
Juglone
medicine.drug
Research Article
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 19420994 and 19420900
- Volume :
- 2020
- Database :
- OpenAIRE
- Journal :
- Oxidative Medicine and Cellular Longevity
- Accession number :
- edsair.doi.dedup.....98d856c6fe81088efb4f08ac7839168e