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Tongxinluo (TXL), a Traditional Chinese Medicinal Compound, Improves Endothelial Function After Chronic Hypoxia Both In Vivo and In Vitro.
- Source :
-
Journal of cardiovascular pharmacology [J Cardiovasc Pharmacol] 2015 Jun; Vol. 65 (6), pp. 579-86. - Publication Year :
- 2015
-
Abstract
- Vascular injury after chronic hypoxia leads to endothelial injury and structural damage to tight junctions (TJs), thereby resulting in a variety of cardiovascular diseases. Thus, attenuating hypoxia-induced damage has great significance for the prevention and treatment of cardiovascular disease. The aim of this study was to investigate whether the endothelial protection conferred by tongxinluo (TXL), a traditional Chinese medicinal compound, is related to its regulation of TJ protein expression. In vivo, we found that TXL could promote hypoxia-induced angiogenesis in lung and liver tissue. In vitro, we found that CoCl2 treatment significantly reduced the expression of the TJ proteins occludin, claudin-1, VE-cadherin, and beta-catenin in cultured human cardiac microvascular endothelial cells. TXL pretreatment abrogated the CoCl2-induced downregulation of these TJ proteins. Conversely, overexpression of Krüppel-like factor 4 (KLF4) inhibited the expression of TJ proteins in human cardiac microvascular endothelial cells, an effect that was reversed by TXL pretreatment. Further experiments showed that TXL could promote endothelial cell proliferation by increasing KLF4 phosphorylation, thereby reversing the effect of KLF4 on the expression of TJ proteins. These findings provide a new molecular mechanism for the TXL-induced increase in TJ protein expression.
- Subjects :
- Animals
Cell Hypoxia
Cell Proliferation drug effects
Cells, Cultured
Chronic Disease
Disease Models, Animal
Dose-Response Relationship, Drug
Endothelial Cells metabolism
Endothelium, Vascular metabolism
Endothelium, Vascular physiopathology
Gene Expression Regulation
Humans
Hypoxia metabolism
Hypoxia physiopathology
Kruppel-Like Factor 4
Kruppel-Like Transcription Factors genetics
Kruppel-Like Transcription Factors metabolism
Male
Mice, Inbred C57BL
Neovascularization, Physiologic drug effects
Phosphorylation
Tight Junction Proteins genetics
Tight Junction Proteins metabolism
Tight Junctions drug effects
Tight Junctions metabolism
Transfection
Angiogenesis Inducing Agents pharmacology
Drugs, Chinese Herbal pharmacology
Endothelial Cells drug effects
Endothelium, Vascular drug effects
Hypoxia drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1533-4023
- Volume :
- 65
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of cardiovascular pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 26065642
- Full Text :
- https://doi.org/10.1097/FJC.0000000000000226