Danlou Tablet Improves Chronic Intermittent Hypoxia-Induced Dyslipidemia and Arteriosclerosis by HIF-1α-Angptl4 mRNA Signaling Pathway.
10.1007/s11655-020-3255-8
- Author:
Jing-Jing TANG
1
;
Guang-Xi LI
1
;
Zhi-Guo LIU
1
;
Rong YI
1
;
Dong YU
2
;
Yue-Bo ZHANG
3
;
Shuang-Qiao ZHAO
4
;
Shi-Han WANG
5
Author Information
1. Department of Pneumology, Guang'anmen Hospital, Chinese Academy of Chinese Medical Sciences, Beijing, 100053, China.
2. Drug Clinical Trial Agency, Guang'anmen Hospital, Chinese Academy of Chinese Medical Sciences, Beijing, 100053, China.
3. Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, 55905, USA.
4. Department of Gynecology, Guang'anmen Hospital, Chinese Academy of Chinese Medical Sciences, Beijing, 100053, China.
5. Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, 55905, USA. wang.shihan@mayo.edu.
- Publication Type:Journal Article
- Keywords:
Chinese medicine;
Danlou Tablet;
angiopoietin-like 4;
arteriosclerosis;
dyslipidemia;
hypoxia-induced factor
- MeSH:
Angiopoietin-Like Protein 4/genetics*;
Animals;
Apolipoproteins E;
Atherosclerosis/metabolism*;
Drugs, Chinese Herbal;
Dyslipidemias/genetics*;
Hypoxia/metabolism*;
Hypoxia-Inducible Factor 1, alpha Subunit/metabolism*;
Mice;
Plaque, Atherosclerotic;
Powders;
RNA, Messenger/genetics*;
Signal Transduction;
Triglycerides;
Water
- From:
Chinese journal of integrative medicine
2022;28(6):509-517
- CountryChina
- Language:English
-
Abstract:
OBJECTIVE:To detect whether Danlou Tablet (DLT) regulates the hypoxia-induced factor (HIF)-1α-angiopoietin-like 4 (Angptl4) mRNA signaling pathway and explore the role of DLT in treating chronic intermittent hypoxia (CIH)-induced dyslipidemia and arteriosclerosis.
METHODS:The mature adipocytes were obtained from 3T3-L1 cell culturation and allocated into 8 groups including control groups (Groups 1 and 5, 0.1 mL of cell culture grade water); DLT groups (Groups 2 and 6, 0.1 mL of 1,000 µg/mL DLT submicron powder solution); dimethyloxalylglycine (DMOG) groups (Groups 3 and 7, DMOG and 0.1 mL of cell culture grade water); DMOG plus DLT groups (Groups 4 and 8, DMOG and 0.1 mL of 1,000 µg/mL DLT submicron powder solution). Groups 1-4 used mature adipocytes and groups 5-8 used HIF-1 α-siRNA lentivirus-transfected mature adipocytes. After 24-h treatment, real-time polymerase chain reaction and Western blot were employed to determine the mRNA and protein expression levels of HIF-1 α and Angptl4. In animal experiments, the CIH model in ApoE-/- mice was established. Sixteen mice were complete randomly divided into 4 groups including sham group, CIH model group [intermittent hypoxia and normal saline (2 mL/time) gavage once a day]; Angptl4 Ab group [intermittent hypoxia and Angptl4 antibody (30 mg/kg) intraperitoneally injected every week]; DLT group [intermittent hypoxia and DLT (250 mg/kg) once a day], 4 mice in each group. After 4-week treatment, enzyme linked immunosorbent assay was used to detect the expression levels of serum total cholesterol (TC) and triglyceride (TG). Hematoxylin-eosin and CD68 staining were used to observe the morphological properties of arterial plaques.
RESULTS:Angptl4 expression was dependent on HIF-1 α, with a reduction in mRNA expression and no response in protein level to DMOG or DLT treatment in relation to siHIF-1 α -transfected cells. DLT inhibited HIF-1 α and Angptl4 mRNA expression (P<0.05 or P<0.01) and reduced HIF-1 α and Angptl4 protein expressions with DMOG in mature adipocytes (all P<0.01), as the effect on HIF-1 α protein also existed in the presence of siHIF-1 α (P<0.01). ApoE-/- mice treated with CIH had increased TG and TC levels (all P<0.01) and atherosclerotic plaque. Angptl4 antibody and DLT both reduce TG and TC levels (all P<0.01), as well as reducing atherosclerotic plaque areas, narrowing arterial wall thickness and alleviating atherosclerotic lesion symptoms to some extent.
CONCLUSION:DLT had positive effects in improving dyslipidemia and arteriosclerosis by inhibiting Angptl4 protein level through HIF-1 α-Angptl4 mRNA signaling pathway.
