Recombinant Thrombomodulin Exerts Anti-autophagic Action in Endothelial Cells and Provides Anti-atherosclerosis Effect in Apolipoprotein E Deficient Mice
Autor: | Guey Yueh Shi, Shi Ya Tseng, Hsing Chun Chung, Kuan Chieh Wang, Hua Lin Wu, Chawn Yau Luo, Po Sheng Chen, Ting-Hsing Chao, Yi-Heng Li |
---|---|
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Apolipoprotein E Science Thrombomodulin ATG5 Biology Models Biological Article 03 medical and health sciences Mice Apolipoproteins E Stress Physiological Autophagy Animals Humans Receptor Fibroblast Growth Factor Type 1 Protein kinase B PI3K/AKT/mTOR pathway Cells Cultured Mice Knockout Multidisciplinary Endothelial Cells Atherosclerosis Recombinant Proteins Disease Models Animal 030104 developmental biology Apoptosis Immunology Cancer research Medicine Signal transduction Signal Transduction |
Zdroj: | Scientific Reports Scientific Reports, Vol 7, Iss 1, Pp 1-9 (2017) |
ISSN: | 2045-2322 |
Popis: | Stress-induced alteration in endothelial cells (ECs) integrity precedes the development of atherosclerosis. Previous studies showed that the soluble recombinant thrombomodulin (rTM) not only increases ECs proliferation but also exerts anti-apoptotic activity in ECs. However, the functional significance of soluble rTM on autophagy-related apoptosis in ECs is still undetermined. Implicating a cytoprotective role for rTM in persistent serum starvation (SS)-induced autophagy in cultured ECs, we found that treatment of rTM decreased the expression of SS-induced autophagy-related proteins, ATG5 and LC3, and the formation of autophagosomes through activation of AKT/mTOR pathway. In addition, treatment of rTM decreased SS-induced EC apoptosis, but this effect of rTM could not be recapitulated by co-treatment with a potent autophagy inducer, rapamycin and in ECs with ATG5 knockdown. In human atherosclerosis specimens, expression of autophagy markers, ATG13 and LC3, were more abundant in aortic intimal ECs with severe atherosclerosis than those without atherosclerosis. Moreover, compared to saline treatment group, administration of rTM reduced LC3 and ATG13 expression, intimal EC apoptosis, and atherosclerotic lesion severity in the aorta of apolipoprotein E deficient mice. In conclusion, treatment with rTM suppressed stress-induced autophagy overactivation in ECs, provided ECs protective effects, and decreased atherosclerosis in apolipoprotein E deficient mice. |
Databáze: | OpenAIRE |
Externí odkaz: |