The protective effect of astragaloside IV against benzo[a]pyrene induced endothelial progenitor cell dysfunction.
OBJECTIVE
Benzo[a]pyrene (BaP), a prominent component of tobacco, has been revealed to induce damage to endothelial progenitor cells (EPCs). Astragaloside IV (AS-IV) is widely used for the treatment of cardiovascular diseases in China. In this study, we evaluated the effects of AS-IV on the function of human EPCs after BaP exposure and explored the underlying mechanism.


METHODS
Human umbilical cord blood mononuclear cells were isolated using density gradient centrifugation. Cells of the 4th passage were randomly divided into 6 groups. EPCs of experimental groups were pre-treated with different concentrations (2, 10 and 50 μg/mL) of AS-IV for 2h before exposure to BaP (20 μM) for 24h. The proliferation, migration, and adhesion of the treated EPCs were evaluated using a cell counting kit-8, Transwell assay and adhesion assay respectively. Interleukin-1β, tumor necrosis factor-α, malondialdehyde and SOD contents in the supernatant were evaluated. The expression of RAGE protein was measured by Western blotting.


RESULTS
The results demonstrated that AS-IV pre-treatment significantly improved BaP-induced dysfunction of EPCs in terms of proliferation, migration and adhesion. Furthermore, AS-IV reduced the production of reactive oxygen species, malondialdehyde, interleukin-1β and tumor necrosis factor-α of the BaP-treated EPCs. Finally AS-IV pre-treated EPCs showed an increased SOD activity and decreased RAGE protein expression.


CONCLUSIONS
AS-IV is able to prevent BaP-mediated EPC dysfunction by at least inhibiting oxidative stress through the RAGE pathway.
Department of Cardiology, The Second Affiliated Hospital, Wenzhou Medical University, Zhejiang Province, Wenzhou 325000, China.
Kangting
K
Ji
Cardiac Care Unit, The First Affiliated Hospital, Wenzhou Medical University, Zhejiang Province, Wenzhou 325000, China.
Jun
J
Chen
Department of Cardiology, The Second Affiliated Hospital, Wenzhou Medical University, Zhejiang Province, Wenzhou 325000, China.
Jianjian
J
Hu
Department of Cardiology, The Second Affiliated Hospital, Wenzhou Medical University, Zhejiang Province, Wenzhou 325000, China.
Yangjing
Y
Xue
Department of Cardiology, The Second Affiliated Hospital, Wenzhou Medical University, Zhejiang Province, Wenzhou 325000, China.
Ripeng
R
Yin
Department of Cardiology, The Second Affiliated Hospital, Wenzhou Medical University, Zhejiang Province, Wenzhou 325000, China.
Qin
Q
Lu
Department of Cardiology, The Second Affiliated Hospital, Wenzhou Medical University, Zhejiang Province, Wenzhou 325000, China.
Wenwu
W
Wu
Department of Cardiology, The Second Affiliated Hospital, Wenzhou Medical University, Zhejiang Province, Wenzhou 325000, China.
Guoqiang
G
Wang
Department of Cardiology, The Second Affiliated Hospital, Wenzhou Medical University, Zhejiang Province, Wenzhou 325000, China.
Xiaoning
X
Wang
Department of Cardiology, The Second Affiliated Hospital, Wenzhou Medical University, Zhejiang Province, Wenzhou 325000, China.
Xifa
X
Song
Department of Cardiology, The Second Affiliated Hospital, Wenzhou Medical University, Zhejiang Province, Wenzhou 325000, China.
Ji
J
Li
Department of Oncology, Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, China. Electronic address: llm@fjtcm.edu.cn.
Lianming
L
Liao
Department of Cardiology, The Second Affiliated Hospital, Wenzhou Medical University, Zhejiang Province, Wenzhou 325000, China. Electronic address: jiftang@126.com.
Jifei
J
Tang
D000704:Analysis of Variance; D001564:Benzo(a)pyrene / Q000009:adverse effects* / Q000032:analysis; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D066026:Endothelial Progenitor Cells / Q000187:drug effects* / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology*; D014026:Nicotiana / Q000737:chemistry*; D014315:Triterpenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C000593871:AGER protein, human; D053583:Interleukin-1beta; D000067759:Receptor for Advanced Glycation End Products; D012503:Saponins; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; D001564:Benzo(a)pyrene; D008315:Malondialdehyde
Astragaloside IV; Benzo[a]pyrene; Endothelial progenitor cells; RAGE