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Resveratrol Ameliorates Atherosclerosis Induced by High-fat Diet and LPS in ApoE-/- Mice and Inhibits the Activation of CD4+ T Cells
Dongping Yuan
Corresponding Author
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Background: Atherosclerosis (AS), which characterized with the accumulation of lipids on the vessel wall, is the pathological basis of many cardiovascular diseases (CVD) and seriously threatens human health. Resveratrol (RES) has been reported to be benefit for AS treatment. This research aimed to observe the effects of RES on AS induced by high-fat diet (HFD) and LPS in ApoE-/- mice and investigate the underlying mechanism.
Methods: ApoE-/- mice were fed with HFD companied with LPS to induce AS and RES was administrated for 20 weeks. Splenic CD4+ T cells were cultured and treated with anti-CD3/CD28 together with LPS, and RES was added. Serum lipids and the atherosclerotic areas of aortas were detected. The activation of CD4+ T cells were investigated both in vivo and in vitro and the expression of DNA methyltransferases (Dnmt) in CD4+ T cells were measured.
Results: In vivo, administration of RES prevented HFD and LPS induced dysfunction of serum lipids including TC (total cholesterol), TG (triglyceride), LDL-C (low density lipoprotein cholesterol) and HDL-C (high density lipoprotein cholesterol), ameliorated the thickened coronary artery wall and decreased the areas of atherosclerotic lesion on aortas. Besides, RES decreased the number of CD4+ T cells in peripheral blood, decreased the expression of CD25 and CD44, but not affected the expression of L-selectin (CD62L). In vitro, RES decreased the expression of Ki67, CD25 and CD44 in CD4+ T cells. Moreover, RES increased the secretion of IL-2, IL-10 and TGF-β1, decreased IL-6. In addition, RES decreased both the mRNA and protein level of Dnmt1 and Dnmt3b in CD4+ T cells.
Conclusion: These results indicated that RES ameliorated AS induced by HFD companied with LPS in ApoE-/- mice, inhibited the proliferation and activation of CD4+ T cells and regulated the expression of Dnmt1 and Dnmt3b.
Keywords
Resveratrol, Atherosclerosis, CD4+ T cells, DNA methyltransferase
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CURRENT STATUS: Under Review
Version 2
Posted 14 May, 2020
No community comments so far
Review #1 received
Received 13 May, 2020
Review #2 received
Received 09 May, 2020
Reviewer #2 agreed
On 06 May, 2020
Reviewers invited
Invitations sent on 05 May, 2020
Reviewer #1 agreed
On 05 May, 2020
Editor assigned
On 30 Apr, 2020
Submission checks complete
On 29 Apr, 2020
Editor invited
On 29 Apr, 2020
No comments provided
Review #2 received
Received 15 Mar, 2020
Editorial decision: Major revision
On 15 Mar, 2020
Review #1 received
Received 09 Mar, 2020
Reviewer #2 agreed
On 05 Mar, 2020
Reviewer #1 agreed
On 25 Feb, 2020
Reviewers invited
Invitations sent on 25 Feb, 2020
Editor assigned
On 20 Feb, 2020
Submission checks complete
On 19 Feb, 2020
Editor invited
On 19 Feb, 2020
First submitted
On 15 Feb, 2020
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This preprint is under consideration at Nutrition & Metabolism. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Resveratrol Ameliorates Atherosclerosis Induced by High-fat Diet and LPS in ApoE-/- Mice and Inhibits the Activation of CD4+ T Cells
Dongping Yuan
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 2
Posted 14 May, 2020
No community comments so far
Review #1 received
Received 13 May, 2020
Review #2 received
Received 09 May, 2020
Reviewer #2 agreed
On 06 May, 2020
Reviewers invited
Invitations sent on 05 May, 2020
Reviewer #1 agreed
On 05 May, 2020
Editor assigned
On 30 Apr, 2020
Submission checks complete
On 29 Apr, 2020
Editor invited
On 29 Apr, 2020
No comments provided
Review #2 received
Received 15 Mar, 2020
Editorial decision: Major revision
On 15 Mar, 2020
Review #1 received
Received 09 Mar, 2020
Reviewer #2 agreed
On 05 Mar, 2020
Reviewer #1 agreed
On 25 Feb, 2020
Reviewers invited
Invitations sent on 25 Feb, 2020
Editor assigned
On 20 Feb, 2020
Submission checks complete
On 19 Feb, 2020
Editor invited
On 19 Feb, 2020
First submitted
On 15 Feb, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Atherosclerosis (AS), which characterized with the accumulation of lipids on the vessel wall, is the pathological basis of many cardiovascular diseases (CVD) and seriously threatens human health. Resveratrol (RES) has been reported to be benefit for AS treatment. This research aimed to observe the effects of RES on AS induced by high-fat diet (HFD) and LPS in ApoE-/- mice and investigate the underlying mechanism.
Methods: ApoE-/- mice were fed with HFD companied with LPS to induce AS and RES was administrated for 20 weeks. Splenic CD4+ T cells were cultured and treated with anti-CD3/CD28 together with LPS, and RES was added. Serum lipids and the atherosclerotic areas of aortas were detected. The activation of CD4+ T cells were investigated both in vivo and in vitro and the expression of DNA methyltransferases (Dnmt) in CD4+ T cells were measured.
Results: In vivo, administration of RES prevented HFD and LPS induced dysfunction of serum lipids including TC (total cholesterol), TG (triglyceride), LDL-C (low density lipoprotein cholesterol) and HDL-C (high density lipoprotein cholesterol), ameliorated the thickened coronary artery wall and decreased the areas of atherosclerotic lesion on aortas. Besides, RES decreased the number of CD4+ T cells in peripheral blood, decreased the expression of CD25 and CD44, but not affected the expression of L-selectin (CD62L). In vitro, RES decreased the expression of Ki67, CD25 and CD44 in CD4+ T cells. Moreover, RES increased the secretion of IL-2, IL-10 and TGF-β1, decreased IL-6. In addition, RES decreased both the mRNA and protein level of Dnmt1 and Dnmt3b in CD4+ T cells.
Conclusion: These results indicated that RES ameliorated AS induced by HFD companied with LPS in ApoE-/- mice, inhibited the proliferation and activation of CD4+ T cells and regulated the expression of Dnmt1 and Dnmt3b.
Figure 1
Figure 2
Figure 3
Figure 4