The Dual Role of NOX4 in Cardiovascular Diseases: Driver of Oxidative Stress and Mediator of Adaptive Remodeling
Round 1
Reviewer 1 Report
The review paper entitled “The dual role of NOX4 in cardiovascular diseases: driver of oxidative stress and mediator of adaptive remodeling” introduced and summarized the roles of NOX4 in heart conditions, such as the development and disease status. The authors well described the complicated functions of NOX4 in the physiological and disease conditions of the heart. However, there are some improvements needed for the review manuscript.
- If possible, please add the detailed NOX4 protein structure and its possible signaling based on the described in chapter 2.
- Although the authors well described the complicated functions of NOX2 in various conditions, it is not well-focused on the authors’ points because there are too many positive and negative effects of NOX4 in the same or different experimental approaches in each chapter. Thus, it is suggested to describe with some direction, for example, the positive effects of NOX4 with cell type differences first, and then the negative effects of NOX4.
- Moreover, it is better to add some discussion about what the difference is in the specific condition in the same model, but with different results.
Author Response
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Author Response File: 
Author Response.pdf
Reviewer 2 Report
The authors present comprehensive data on the role of NOX4 in cardiovascular diseases. The overview of the literature is complete and up-to-date. The collected informations are timely and interesting for the scientific community. Chapter 5 which intends to explain the contradictory and highly complex data on the deleterious and beneficial cardiac effects of Nox4 is interesting and highlights important aspects. Some of the conclusions presented in the chapters might be more relevant and better fitted in the Conclusions e.g. page 18. lines 397-404).
The informations included in the six chapters are somehow redundant. For example chapter 4 and 6 could have been combined and shortened. ble 5. and 6. shows up at pages 6 and 7 followed by the Tables 1-4 later, which should be corrected by replacing or renumbering. Moreover repetitive informations are presented again in the tables as well. For example Table 4 Heart failure and Myocardial ischemia compare it with Table 1 Heart failure and Myocardial ischemia. What is the rationale behind separating the Nox4 Tg mice strains in different tables? Both describes beneficial roles!The desciption of the Nox4 splice variants (page 25 lines 717-756) might be replaced under 2.1 gene structure.
Author Response
Please see the attachment.
Author Response File: Author Response.pdf
Round 2
Reviewer 2 Report
The revised manuscript clarified and corrected all items which were criticized in the original version. The result is interesting for the scientist working on the field and might attract to read it scientist who deals with similar issues on other fields. Clinicians might be interested as well. The conclusion chapter highlights some unresolved questions and technical issues.
No further need to change in the text
