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Research article
Hydroxyurea Regressed Atherosclerosis Plaques in ApoE-/- mice: A Discovery Based on Clinic
Yan Wang
Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Materia Medica
Corresponding Author
ORCiD: https://orcid.org/0000-0001-7924-4988
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: A 58-year-old lady was introduced to the clinic because of acute coronary syndrome combined with essential thrombocythemia. After treating her with aspirin, statins and hydroxyurea (HU), the plaques in her coronary arteries showed improvement dramatically. Here, we aim to investigate that whether HU reduces atherosclerosis plaques in ApoE-/- mice.
Methods: Wild-type (C57BL/6, n=8) and Apolipoprotein E knockout (ApoE-/-, n=40) mice were used in atherosclerosis model and medication groups. The mice were separated into 7 groups, including the normal control group, the atherosclerosis model group, the dual antiplatelet therapy group (aspirin, and clopidogrel bisulfate), the low-dose and high-dose HU therapy groups [aspirin, clopidogrel bisulfate, and HU (10 or 20 mg/kg/day)], the positive medicine group (aspirin, clopidogrel bisulfate, and atorvastatin calcium), and the combined medicine treatment group [aspirin, clopidogrel bisulfate, atorvastatin calcium, and HU (10 mg/kg/day)]. Fasting serum and aortic vessels were obtained after experiment. The aortic oil red O, hematoxylin-eosin (H&E), and full-length oil red O staining were performed to evaluate the HU’s efficacy of anti- atherosclerosis, and the blood lipid / glucose levels and liver /kidney functions were evaluated after HU treatment.
Results: The oil red O and H&E staining results came out that HU therapy with antiplatelet showed an obvious effect in decreasing atherosclerosis plaques and the effect of HU therapy (10 or 20 mg/kg) was stronger than dual antiplatelet therapy plus statin, without liver and kidney toxicity observed. Furthermore, the combined drugs with HU (10 mg/kg/day), statin and antiplatelet nearly eliminated the plaques.
Conclusions: A discovery based on clinic reveals that HU regressed atherosclerosis plaques in ApoE-/- mice, which provides us a new insight into anti-atherosclerosis drugs strategy.
Keywords
Hydroxyurea (HU), Atherosclerosis, Clinical based, ApoE-/- mice, Pharmacodynamics
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This is a preprint. It has not completed peer review.
Research article
Hydroxyurea Regressed Atherosclerosis Plaques in ApoE-/- mice: A Discovery Based on Clinic
Yan Wang
Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Materia Medica
Corresponding Author
ORCiD: https://orcid.org/0000-0001-7924-4988
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 17 Sep, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: A 58-year-old lady was introduced to the clinic because of acute coronary syndrome combined with essential thrombocythemia. After treating her with aspirin, statins and hydroxyurea (HU), the plaques in her coronary arteries showed improvement dramatically. Here, we aim to investigate that whether HU reduces atherosclerosis plaques in ApoE-/- mice.
Methods: Wild-type (C57BL/6, n=8) and Apolipoprotein E knockout (ApoE-/-, n=40) mice were used in atherosclerosis model and medication groups. The mice were separated into 7 groups, including the normal control group, the atherosclerosis model group, the dual antiplatelet therapy group (aspirin, and clopidogrel bisulfate), the low-dose and high-dose HU therapy groups [aspirin, clopidogrel bisulfate, and HU (10 or 20 mg/kg/day)], the positive medicine group (aspirin, clopidogrel bisulfate, and atorvastatin calcium), and the combined medicine treatment group [aspirin, clopidogrel bisulfate, atorvastatin calcium, and HU (10 mg/kg/day)]. Fasting serum and aortic vessels were obtained after experiment. The aortic oil red O, hematoxylin-eosin (H&E), and full-length oil red O staining were performed to evaluate the HU’s efficacy of anti- atherosclerosis, and the blood lipid / glucose levels and liver /kidney functions were evaluated after HU treatment.
Results: The oil red O and H&E staining results came out that HU therapy with antiplatelet showed an obvious effect in decreasing atherosclerosis plaques and the effect of HU therapy (10 or 20 mg/kg) was stronger than dual antiplatelet therapy plus statin, without liver and kidney toxicity observed. Furthermore, the combined drugs with HU (10 mg/kg/day), statin and antiplatelet nearly eliminated the plaques.
Conclusions: A discovery based on clinic reveals that HU regressed atherosclerosis plaques in ApoE-/- mice, which provides us a new insight into anti-atherosclerosis drugs strategy.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5