Format

Send to

Choose Destination
J Mol Endocrinol. 2019 Jul 1;63(1):27-38. doi: 10.1530/JME-19-0018.

Indazole-Cl inhibits hypoxia-induced cyclooxygenase-2 expression in vascular smooth muscle cells.

Author information

1
Department of Integrative Bioscience and Biotechnology, College of Life Science, Sejong University, Seoul, Korea.
2
Division of Functional Food Research, Korea Food Research Institute, Jeollabuk-do, Korea.
3
Department of Obstetrics, Gynecology and Women's Health, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
4
Department of Biomedical Engineering, College of Medicine, Kyung Hee University, Seoul, Korea.

Abstract

Atherosclerosis is the most common root cause of arterial disease, such as coronary artery disease and carotid artery disease. Hypoxia is associated with the formation of macrophages and increased inflammation and is known to be present in lesions of atherosclerotic. Vascular smooth muscle cells (VSMCs) are one of the major components of blood vessels, and hypoxic conditions affect VSMC inflammation, proliferation and migration, which contribute to vascular stenosis and play a major role in the atherosclerotic process. Estrogen receptor (ER)-β is thought to play an important role in preventing the inflammatory response in VSMCs. In this report, we studied the anti-inflammatory effect of indazole (In)-Cl, an ERβ-specific agonist, under conditions of hypoxia. Expression of cyclooxygenase-2 reduced by hypoxia was inhibited by In-Cl treatment in VSMCs, and this effect was antagonized by an anti-estrogen compound. Additionally, the production of reactive oxygen species induced under conditions of hypoxia was reduced by treatment with In-Cl. Increased cell migration and invasion by hypoxia were also dramatically decreased following treatment with In-Cl. The increase in cell proliferation following treatment with platelet-derived growth factor was attenuated by In-Cl in VSMCs. RNA sequencing analysis was performed to identify changes in inflammation-related genes following In-Cl treatment in the hypoxic state. Our results suggest that ERβ is a potential therapeutic target for the suppression of hypoxia-induced inflammation in VSMCs.

KEYWORDS:

COX-2; ER beta; VSMC; hypoxia

PMID:
31075756
DOI:
10.1530/JME-19-0018

Supplemental Content

Full text links

Icon for Sheridan PubFactory
Loading ...
Support Center