Molecular Pathophysiology of Chronic Thromboembolic Pulmonary Hypertension: A Clinical Update from a Basic Research Perspective
, Guillermo Cueto-Robledo 2, Dulce Iliana Navarro-Vergara 2, Maria Berenice Torres-Rojas 2, Marisol GarcÃa-Cesar 2, Oscar Pérez-Méndez 4,5 and Galileo Escobedo 1,*
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsThis is a broad review with a solid outline and rich content. Only a few minor revisions are needed before publication.
The molecular pathophysiology is missing in the current version. The authors should consider using a molecular network to illustrate the pathophysiology of CTEPH.
Author Response
REVIEW REPORT
Reviewer 1
Query (Q) 1. This is a broad review with a solid outline and rich content. Only a few minor revisions are needed before publication.
Response (R) 1. Thank you for your kind comments on our work. We considered all your comments and made several changes to the manuscript text. Please find below these modifications point-by-point.
Q2. The molecular pathophysiology is missing in the current version. The authors should consider using a molecular network to illustrate the pathophysiology of CTEPH.
R2. We added an entirely new paragraph with more references to explain the molecular pathophysiology of CTEPH and drew a new figure to illustrate it. Please find these changes marked yellow on page 8 and in new figure 3.
We thank you for the comments and suggestions that have indubitably improved the last version of our work.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
Comments and Suggestions for AuthorsAll comments are added on the pdf file of the manuscript
Comments for author File: Comments.pdf
Author Response
REVIEW REPORT
Reviewer 2
Query (Q) 1. Line 94. Figure containing summary of the molecular mechanisms associated with the development of chronic thromboembolic pulmonary hypertension will add more value to the manuscript.
Response (R) 1. We drew a new figure to illustrate the molecular mechanisms behind CTEPH development. Please find this addition in new figure 4, page 13.
Q2. Table 1. Write full form then add abbreviations of each component.
R2. We wrote full definitions for each mediator before using abbreviations. Please find this modification marked green on pages 3-5.
Q3. Line 126. Risk factors can be presented in pictorial diagram.
R3. We drew a new figure to illustrate the risk factors of CTEPH. Please find this addition in new figure 1, page 6.
Q4. Line 154. Both headings seems to be the same, 4. CTEPH pathophysiology and 5. Disease mechanisms of CTEPH seems to be the same thing.
R4. We substantially changed Chapter 4 – CTEPH pathophysiology—by adding a new paragraph with more references, with the aim of making a clear distinction between it and Chapter 5. Now, Chapter 5 is focused on CTEPH pathophysiology, whereas Chapter 6 emphasizes only molecular mechanisms involved in disease progression. Please find these changes marked yellow on pages 7, 8, and 10-13.
Q5. A pictorial presentation of pulmonary pathway from heart to lungs and its diseased mechanism will elaborate the pathophysiology as compared to Fig. 1.
R5. We drew a new figure to illustrate the circulatory network between lungs and heart in the setting of CTEPH pathophysiology. Please find this addition in new figure 2, page 8.
Q6. Study is talking more on pathophysiology but a section containing diagnostic technique will add more colors to manuscript.
R6. Following the Reviewer’s suggestion, we added an entirely new Chapter describing diagnostic techniques for diagnosing CTEPH. Please find this addition marked pink on page 7.
We thank you for your suggestions and observations, which have indubitably improved the last version of the manuscript.
Author Response File: Author Response.pdf
Reviewer 3 Report
Comments and Suggestions for AuthorsDear Authors,
Your review on "Molecular Pathophysiology of Chronic Thromboembolic Pulmonary Hypertension: A clinical update from a basic research perspective" is in general well written regarding scientific aspects and format.
My comments:
1. The Table 1 should be revised regarding format.
2. I recommend to add 1-2 more figures regarding the pathophysiology of CTEPH to make the review more attractive and more easily read.
3. Please check and write all references according to the reference writing style used in this journal.
Comments on the Quality of English LanguageEnglish of the manuscript should be carefully checked and improved.
Author Response
REVIEW REPORT
Reviewer 3
Query (Q) 1. Your review on "Molecular Pathophysiology of Chronic Thromboembolic Pulmonary Hypertension: A clinical update from a basic research perspective" is in general well written regarding scientific aspects and format.
Response (R) 1. We thank the Reviewer for her/his kind comments on our work.
Q2. The Table 1 should be revised regarding format.
R2. We revised Table 1’s format following the journal’s guidelines. Please find these modifications marked green on pages 3-5.
Q3. I recommend to add 1-2 more figures regarding the pathophysiology of CTEPH to make the review more attractive and more easily read.
R3. Following your recommendation, we drew three entirely new figures illustrating CTEPH pathophysiology, the molecular bases of the disease, and the cardiopulmonary circulatory network involved in its progression. Please find these changes in new figures 1, 2, 3, and 4, pages 6, 8, 9, and 13.
Q4. Please check and write all references according to the reference writing style used in this journal.
R4. We double-checked all references and corrected all inconsistencies to conform to the journal’s reference style. These changes are marked turquoise on pages 14-22.
Q5. English of the manuscript should be carefully checked and improved.
R5. We revised the English of the manuscript, correcting grammar, punctuation, and tone. You can see these edits and changes all along the manuscript.
Author Response File: Author Response.pdf
