Wnt Signaling in Atherosclerosis: Mechanisms to Therapeutic Implications
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsThis manuscript review the possible role of Wnt signaling in atherosclerosis and its potential for therapeutic applications. It is nicely written and provide a good overview on such a complex pathway. My main comments are why Figure 2 focus only on endothelial cells and why in the conclusion, the authors seems to favor the endothelial cell as a therapeutic site. Moreover, although there are some mentions of possible therapeutic targets in macrophages, I believe there should be a section describing what is known about Wnt signaling in macrophages in relation to atherosclerosis.
Minor comment. There are some typos.
Proteosome should be changed to proteasome
All appearances (including Fig. 2) of p66Sch should be changed to p66Shc
Line 201 “Wnt4 upregulation activates Wnt/β-catenin pathway in stimulates the proliferation of VSMCs during…” should probably be “Wnt4 upregulation activates Wnt/β-catenin pathway and stimulates the proliferation of VSMCs during…”
Line 347. CRSPR-Cas9 should be “CRISPR-Cas9”
Comments on the Quality of English LanguageNicely written.
Author Response
Reviewer 1
Comment 1: This manuscript review the possible role of Wnt signaling in atherosclerosis and its potential for therapeutic applications. It is nicely written and provide a good overview on such a complex pathway. My main comments are why Figure 2 focus only on endothelial cells and why in the conclusion, the authors seems to favor the endothelial cell as a therapeutic site. Moreover, although there are some mentions of possible therapeutic targets in macrophages, I believe there should be a section describing what is known about Wnt signaling in macrophages in relation to atherosclerosis.
Response: Thanks for this comment. We have added a brief section about Wnt signaling in macrophages on pages 8-9.
Comment 2: Minor comment. There are some typos.
Proteosome should be changed to proteasome
All appearances (including Fig. 2) of p66Sch should be changed to p66Shc
Line 201 “Wnt4 upregulation activates Wnt/β-catenin pathway in stimulates the proliferation of VSMCs during…” should probably be “Wnt4 upregulation activates Wnt/β-catenin pathway and stimulates the proliferation of VSMCs during…”
Line 347. CRSPR-Cas9 should be “CRISPR-Cas9”
Response: Thanks for this comment. All the mentioned typos are now corrected and highlighted in the corrected manuscript.
Comment 3: Comments on the Quality of English Language: Nicely written.
Response: Thank you.
Reviewer 2 Report
Comments and Suggestions for AuthorsReviewer report Biomedicines
Wnt signaling in atherosclerosis: mechanisms to therapeutic implications
This is a well-written article that elaborates on the role of the WNT pathway in atherosclerosis.
1. Please elaborate the potential strategies in diagram form to make it more understandable to readers.
2. How wnt Pathway take part in cholesterol trafficking and maintenance please explain.
3.The authors have not mentioned proper information about supplementary malarial, if supplementary material is available, please mention it.
4. Please mention about author's contribution, funding source, institutional review board statement, informed consent statement, data availability statement, acknowledgment, and conflicts of interest if any.
5. Please mention two distinct types of wnt non-canonical pathways Planar cell polarity (PCP) and Wnt/Ca2+ signaling diagrammatically.
Author Response
Reviewer 2
Wnt signaling in atherosclerosis: mechanisms to therapeutic implications
This is a well-written article that elaborates on the role of the WNT pathway in atherosclerosis.
Comment 1: Please elaborate the potential strategies in diagram form to make it more understandable to readers.
Response: Thanks for the comment. We already have a table (table 1) for this section (5.1. Potential strategies to target Wnt pathway). If we add a diagram for the same section, we think that would be too repetitive.
Comment 2: How wnt Pathway take part in cholesterol trafficking and maintenance please explain.
Response: Thanks for the comment. We have added a section about Wnt pathway in cholesterol storage and trafficking on page 9.
Comment 3: The authors have not mentioned proper information about supplementary malarial, if supplementary material is available, please mention it.
Response: We have mentioned “Not applicable” in the supplementary material section of the revised manuscript.
Comment 4: Please mention about author's contribution, funding source, institutional review board statement, informed consent statement, data availability statement, acknowledgment, and conflicts of interest if any.
Response: We have updated the above-mentioned sections in the revised manuscript.
Comment 5: Please mention two distinct types of wnt non-canonical pathways Planar cell polarity (PCP) and Wnt/Ca2+ signaling diagrammatically.
Response: We have revised figure 1 according to the reviewer’s comment.
Reviewer 3 Report
Comments and Suggestions for AuthorsThe manuscript entitled, Wnt Signaling in Atherosclerosis: Mechanisms to Therapeutic Implications, is interesting and well written. This review compiled the molecular mechanism of Wnt signaling in vascular endothelial cells and vascular smooth muscle cells in the pathophysiology of atherosclerosis. It also discussed the therapeutic implications of Wnt signaling as a potential target to treat atherosclerosis. Although this review is well-organized and well-written, I would appreciate seeing some changes in the manuscript as follows:
Major Concerns:
1. Figure 2: What are the upstream targets of Cox-2, IL-8, IL-4, NOX and P66? In this cartoon, it's essential to mention the upstream signaling molecules (receptor-associated intracellular factors and subsequent downstream targets).
2. Including a cartoon of Wnt signaling in SMCs will make the review more attractive and friendly to the readers.
Comments on the Quality of English LanguageThe quality of the English is nice except for some typos.
Author Response
Reviewer 3
The manuscript entitled, Wnt Signaling in Atherosclerosis: Mechanisms to Therapeutic Implications, is interesting and well written. This review compiled the molecular mechanism of Wnt signaling in vascular endothelial cells and vascular smooth muscle cells in the pathophysiology of atherosclerosis. It also discussed the therapeutic implications of Wnt signaling as a potential target to treat atherosclerosis. Although this review is well-organized and well-written, I would appreciate seeing some changes in the manuscript as follows:
Major Concerns:
Comment 1: Figure 2: What are the upstream targets of Cox-2, IL-8, IL-4, NOX and P66? In this cartoon, it's essential to mention the upstream signaling molecules (receptor-associated intracellular factors and subsequent downstream targets).
Response: We have revised figure 2 according to the reviewer’s comment. The figure legend is also updated, and a sentence is added to the main text body (page 4, line 170-172). All the changes are highlighted in the revised manuscript.
Comment 2: Including a cartoon of Wnt signaling in SMCs will make the review more attractive and friendly to the readers.
Response: We have added a new figure (figure 3) in the revised manuscript.
Comment 3: Comments on the Quality of English Language: The quality of the English is nice except for some typos.
Response: Thank you. Typos are carefully checked and corrected. All the changes are highlighted in the revised manuscript.
