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The Influence of Hyperlipidemia on Endothelial Function of FPN1 Tek-Cre Mice and the Intervention Effect of Tetramethylpyrazine
- Source :
- Cellular Physiology and Biochemistry, Vol 47, Iss 1, Pp 119-128 (2018)
- Publication Year :
- 2017
-
Abstract
- Background/Aims: Systemic iron homeostasis is strictly governed in mammals; however, disordered iron metabolism (such as excess iron burden) is recognized as a risk factor for various types of diseases including AS (Atherosclerosis). The hepcidin-ferroportin axis plays the key role in regulation of iron homeostasis and modulation of this signaling could be a potential therapeutic strategy in the treatment of these diseases. TMP (Tetramethylpyrazine) has been reported to have therapeutical effect on AS. Here, we aimed to investigate the effect of iron overload under hyperlipidemia condition on the endothelial injury, inflammation and oxidative stress by employing FPN1 Tek-cre mouse model with or without TMP intervention. Methods: Subjects for this study were 80 FPN1 Tek-cre mice and 40 C57BL/6 mice and we randomly divided them into six groups: Group N: C57BL/6 mice with normal diet, Group M: C57BL/6 mice with high-fat diet, Group FN: FPN1 Tek-cre mice with normal diet, Group FNT: FPN1 Tek-cre mice with normal diet and TMP injection, Group FM: FPN1 Tek-cre mice with high-fat diet, Group FMT: FPN1 Tek-cre mice with high-fat diet and TMP injection. After seven days of treatment, blood samples were obtained to detect the levels of blood lipids, Hepcidin, NO, ET-1, ROS, MDA, SOD, IL-1, IL-6 and TNF-α respectively. The liver and aorta were used for testing the lipid deposition by using hematoxylin and eosin(HE). Results: Hyperlipidemia could cause iron overload in the aorta and increased serum hepcidin level, particularly in FPN1 Tek-cre mice, and can be reversed by TMP intervention. Knockout of Fpn1 induced increase of serum hepcidin, exacerbated endothelial dysfunction, oxidative stress and inflammatory response, particularly under hyperlipidemia condition. TMP intervention attenuated these processes. Conclusions: Our study signifies the potential application of certain natural compounds to ameliorating iron disorders induced by hyperlipidemia and protecting on endothelial function through modulation of hepcidin-ferroportin signaling.
- Subjects :
- 0301 basic medicine
Male
Physiology
Ferroportin
Hepcidin
Blood lipids
medicine.disease_cause
lcsh:Physiology
Antioxidants
chemistry.chemical_compound
0302 clinical medicine
Hyperlipidemia
Tetramethylpyrazine
lcsh:QD415-436
Endothelial dysfunction
Cation Transport Proteins
Aorta
biology
Tek-cre FPN1 mice
lcsh:QP1-981
Pyrazines
Female
medicine.medical_specialty
Iron Overload
Normal diet
Iron
Hyperlipidemias
Endothelin
lcsh:Biochemistry
03 medical and health sciences
Hepcidins
Internal medicine
medicine
Animals
business.industry
Endothelial Cells
Endothelial function
medicine.disease
Atherosclerosis
Mice, Inbred C57BL
Oxidative Stress
030104 developmental biology
Endocrinology
chemistry
biology.protein
business
030217 neurology & neurosurgery
Oxidative stress
Drugs, Chinese Herbal
Subjects
Details
- ISSN :
- 14219778
- Volume :
- 47
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
- Accession number :
- edsair.doi.dedup.....798fad3e7c901e714d03e0277c649e88