Vascular NADPH Oxidases and Atherothrombotic Stroke
Round 1
Reviewer 1 Report
Comments and Suggestions for Authorsthe topic is really intersting
I think the authors needs to review new literature data, because some bibliographic researches are too old ( longer than 10 years)
maybe the amyloidosis and the role of systemic inflammation ( chronic diseases- rheumatic, gastrointestinal ) must be discussed because the atherosclerotic process is even more rapid in this population, it is not recommended to be neglected.
the figures are very nice designed.
Author Response
Comment 1:
The topic is really intersting
I think the authors needs to review new literature data, because some bibliographic researches are too old (longer than 10 years)
Response 1:
Thank you very much for your comment. Now, 20 references have been updated, changed or eliminated in the whole manuscript. We have addressed this comment from two different scopes.
On the one hand:
- We have focused on updating 4 references of the section “ Introduction”. References 1, 4, 6 and 7 of the older version of the manuscript have changed.
- We have updated 6 references related with NOX activity in endothelial cells and inflammation through different proinflammatory mediators (please see lines 132-145).
- Similarly, 7 references concerning the role of NOX homologues in VSMCs proliferation and migration have been updated (please see lines 189-198, lines 201-203 and lines 232-235).
- The other changes have been made along the manuscript. For instance: lines 246-248 and lines 323-325.
On the other hand:
- In the section “2. NADPH oxidases in the vessel wall” we would like to maintain those papers that described for the first time the expression and localization of the NOXs in the vessel wall (ref.), citing the original articles.
- In the section “4.1 NADPH oxidases, BBB disruption and stroke” two references concerning NOX1 in MCAO models have been maintained even though they are from 2009-2010 (please see lines 298-299). This is because no more studies have been made relating NOX1 and MCAO models of stroke and we state that the implications of this oxidase in this stage of the diseases are limited.
Comment 2: maybe the amyloidosis and the role of systemic inflammation ( chronic diseases- rheumatic, gastrointestinal ) must be discussed because the atherosclerotic process is even more rapid in this population, it is not recommended to be neglected.
Response 2: We really appreciate your comment. We have now added a new paragraph at the end of section “3.1 NADPH oxidases and endothelial dysfunction” (please see lines 148-164). In this text fragment we discuss the role of chronic inflammatory diseases in the risk of atherosclerosis development and how ROS and NOX activity can increase this new source of inflammation contributing to the disease. We have now renamed the section with the title “3.1 NADPH oxidases, endothelial dysfunction, and inflammation” to make it more suitable to the main text.
Comment 3: the figures are very nice designed.
Response 3: Thank you very much for your kind comments.
Reviewer 2 Report
Comments and Suggestions for AuthorsI have received for review a review entitled “Vascular NADPH oxidases and atherothrombotic stroke” which is being processed for publication by Stresses.
The manuscript proposed by the authors brings into discussion an interesting topic, but authors should discuss the following aspects:
Abstract
- well structured
The manuscript is systematized in a coherent way that attracts the reader.
I congratulate the authors for the iconography used, one of the best I've seen lately in review articles.
Section 3.1 - are there human studies?
I suggest introducing an additional section addressing future research directions in this area, including proposals from the authors
Conclusions - summarize the main data presented in the manuscript content.
In conclusion, the proposed manuscript is a very interesting one, with future clinical and therapeutic implications.
Author Response
Comment 1: I have received for review a review entitled “Vascular NADPH oxidases and atherothrombotic stroke” which is being processed for publication by Stresses.
The manuscript proposed by the authors brings into discussion an interesting topic, but authors should discuss the following aspects:
Abstract
- well structured
The manuscript is systematized in a coherent way that attracts the reader.
I congratulate the authors for the iconography used, one of the best I've seen lately in review articles.
Response 1: Thank you very much for your kind comments.
Comment 2: Section 3.1 - are there human studies?
Response 2: Thank you. There are human studies that analyze the endothelial dysfunction and its value as a marker of CVDs prognostic. There is limited information when this is tried to be related with NOXs. We have added a first paragraph in the section “3.1 NADPH oxidases, endothelial dysfunction, and inflammation”. In this new fragment of the text, we discussed how endothelial dysfunction is related with cardiovascular diseases and atherosclerosis in human patients. Please see lines 106-111. As there is a limited availability of NOX inhibitors, there is scarce information about how these molecules may or not improve endothelial dysfunction in patients suffering from CVDs.
Comment 3: I suggest introducing an additional section addressing future research directions in this area, including proposals from the authors
Response 3: Thank you for your comment. We have now added a specific section for future perspectives in which we have explained in more detail the future research directions in this area. We have proposed the use of more complex in vitro systems, as well as the use of drug delivery systems and the development of isoform-specific inhibitors. Please see lines 401-430.
Comment 4: Conclusions - summarize the main data presented in the manuscript content.
Response 4: We really appreciate your comment. We have modified the section “5. Conclusions” providing a more detailed summary about NOX implications in each stage of atherosclerosis separated from the future considerations and perspectives, please see lines 381-399.
Comment 5: In conclusion, the proposed manuscript is a very interesting one, with future clinical and therapeutic implications.
Response 5: Thank you very much.
Round 2
Reviewer 1 Report
Comments and Suggestions for Authorsthe authors answerred to all querries
Good luck
