scholarly journals GW25-e5361 Traditional Chinese medicine Tongxinluo inhibits ischemia/reperfusion induced apoptosis of human cardiac microvascular endothelial cells via activating the RISK pathways

2014 ◽  
Vol 64 (16) ◽  
pp. C32
Author(s):  
Cui Hehe ◽  
Li Xiangdong ◽  
Qi Kang ◽  
Li Qing ◽  
Yang Yuejin
2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Hehe Cui ◽  
Xiangdong Li ◽  
Zhigang Wang ◽  
Na Li ◽  
Kang Qi ◽  
...  

Cardiac microvascular endothelial cells (CMECs) regulate the function of cardiomyocytes and blood cells in myocardial ischemia/ reperfusion injury (MIRI) via paracrine methods. Tongxinluo (TXL) is a Traditional Chinese Medicine compound to treat angina pectoris in China, which is constituted of ginseng and other 11 natural products. It is proved to improve the endothelial function and be protective against MIRI. Thus, we aimed to find alterations in paracrine function of CMECs under the hypoxia/reoxygenation (H/R) situation and its modulation by TXL. CMECs were exposed to different concentrations of TXL for 30 min and then subjected to H/R for 12 h/2 h. Apoptotic rates were measured to determine the optimal concentration. Protein antibody arrays were used to find the alterations of cytokines in conditioned medium (CM) secreted by CMECs. Gene Ontology project was adopted to describe the functions of changed cytokines. TXL inhibited apoptosis of CMECs dose-dependently under H/R and reached its peak effect at 800 μg/mL. Thirty-three types of cytokines were significantly changed by H/R (19 factors decreased and 14 increased), and TXL at 800μg/ml changed 121 types of cytokines compared to the H/R group (93 factors decreased and 28 increased). The cytokines with significant alterations were involved in cell differentiation and proliferation, positive chemotaxis, and endothelial cell migration. Among these cytokines, bFGF, PDGF and IL-7 were attenuated by H/R and further decreased by TXL, while IL-21, MCP-2 and GROa were increased by H/R but decreased by TXL. The study elucidated the paracrine function of CMECs in MIRI and partly illuminated the protective mechanisms of TXL.


2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Qing Li ◽  
Yuejin Yang

Background: Proteomics is a potential tool to study the large-scale expression, function and interaction of the complement of proteins in an organism. In this study, we used the TMT-labeled proteomics to detect the various cytokines in an in vitro model of cardiac microvascular endothelial cells (CMECs) ischemia/reperfusion injury with Tongxinluo(TXL) treatment. Our aims are to investigate whether TXL could modulate the secretion function of CMECs, and to synthetically analysis the underlying mechanism of the regulation. Methods: Human CMECs were exposed to different concentrations of TXL, and incubated to scavenge free oxygen for 2 h of hypoxia and were moved to normal conditions for 2 h of reoxygenation. Cell apoptosis was assessed by flow cytometric analysis. CMECs were divided into three groups for TMT-labeled proteomics analysis: CMECs in normal condition (Group N), CMECs in hypoxia and serum deprivation condition (Group HR), CMECs treatment with TXL in hypoxia and serum condition(Group HR+TXL) . We utilized bioinformatics analysis to identify differential proteins. Results: TXL concentration-dependently decreased apoptosis of CMECs. The optimal concentration of TXL to have the maximum protection for CMECs was 800 μg/mL. Both hypoxia/reoxygenation and TXL treatment significantly changed the cytokines level of CMECs. 32 differential proteins between group N and group HR were detected. TXL treatment up-regulated 6 cytokines and down-regulated 6 cytokines in ischemia/reperfusion injury. These proteins mainly had vital functions such as cell proliferation, stress response, regulation of multicelluler organismal metabolic process. We evaluated several proteins played important roles in ischemia/reperfusion injury including Human Heme Oxygenase 1 (HMOX1), angiopoietin 2 (ANGPT2), sequestosome 1 (SQSTM1), and connective tissue growth factor (CTGF). Conclusion: The study presented differential proteins responsible for ischemia/reperfusion injury through TMT-labeled proteomic analysis. We assessed some vital proteins including their characters and roles. These findings may provide new mechanisms of TXL treatment in acute myocardial diseases.


2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Zhu Hai-Yan ◽  
Gao Yong-Hong ◽  
Wang Zhi-Yao ◽  
Xu Bing ◽  
Wu Ai-Ming ◽  
...  

Astragalus polysaccharide is a major component of radix astragali, a vital qi-reinforcing herb medicine with favorable immune-regulating effects. In a previous animal experiment, we demonstrated that astragalus polysaccharide effectively alleviates ischemia-reperfusion injury (IRI) of cardiac muscle through the regulation of the inflammatory reactions. However, the relationship between this herb and the cohesion molecules on the cell surface remains controversial. In this study, human cardiac microvascular endothelial cells (HCMECs) were used to validate the protective effects of astragalus under an IRI scheme simulated through hypoxia/reoxygenation in vitro. The results indicated that astragalus polysaccharide inhibited the cohesion between HCMECs and polymorphonuclear leukocyte (PMN) during IRI through the downregulation of p38 MAPK signaling and the reduction of cohesive molecule expression in HCMECs.


2017 ◽  
Vol 41 (4) ◽  
pp. 1503-1518 ◽  
Author(s):  
Qing Li ◽  
He-He Cui ◽  
Yue-Jin Yang ◽  
Xiang-Dong Li ◽  
Gui-Hao Chen ◽  
...  

Background: The protection of endothelial cells (ECs) against reperfusion injury has received little attention. In this study, we used Tandem Mass Tag (TMT) labeling proteomics to investigate the modulated proteins in an in vitro model of cardiac microvascular endothelial cells (CMECs) subjected to ischemia/reperfusion (I/R) injury and their alteration by traditional Chinese medicine Tongxinluo (TXL). Methods: Human CMECs were subjected to 2 h of hypoxia followed by 2 h of reoxygenation with different concentrations of TXL Protein expression profiles of CMECs were determined using tandem mass spectrometry. We evaluated several proteins with altered expression in I/R injury and summarized some reported proteins related to I/R injury. Results: TXL dose-dependently decreased CMEC apoptosis, and the optimal concentration was 800 µg/mL. I/R significantly altered proteins in CMECs, and 30 different proteins were detected between a normal group and a hypoxia and serum deprivation group. In I/R injury, TXL treatment up-regulated 6 types of proteins including acyl-coenzyme A synthetase ACSM2B mitochondrial (ACSM2B), cyclin-dependent kinase inhibitor 1B (CDKN1B), heme oxygenase 1 (HMOX1), transcription factor SOX-17 (SOX17), sequestosome-1 isoform 1 (SQSTM1), and TBC1 domain family member 10B (TBC1D10B). Also, TXL down-regulated 5 proteins including angiopoietin-2 isoform c precursor (ANGPT2), cytochrome c oxidase assembly factor 5 (COA5), connective tissue growth factor precursor (CTGF), cathepsin L1 isoform 2 (CTSL), and eukaryotic elongation factor 2 kinase (LOC101930123). These types of proteins mainly had vital functions, including cell proliferation, stress response, and regulation of metabolic process. Conclusions: The study presented differential proteins upon I/R injury through a proteomic analysis. TXL modulated the expression of proteins in CMECs and has a protective role in response to I/R.


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