Cardioprotective Mechanisms against Reperfusion Injury in Acute Myocardial Infarction: Targeting Angiotensin II Receptors

Round 1

Reviewer 1 Report

A very good work.

Author Response

The authors are thankul for your comment

Reviewer 2 Report

This review article by Gabriel et al, is well written and gives a nice overview of Angiotensin II receptors, its involvement in Renin-Angiotensin-System (RAS) leading to reperfusion injury in heart following PCI primarily via Reactive Oxygen Species (ROS). I have few comments and suggestions for the authors.

1.      Authors state in their review article that PKCε is a protein responsible for the translocation of AT1R and AT2R from the plasma membrane to the mitochondrial membrane. However, in Figure 1, authors are showing the translocation of AT2R from plasma membrane to nucleus and then from nucleus to mitochondrial membrane. For the benefit of readers, authors should clarify this statement either by adding text in the review or modifying their Figure 1 (as shown for AT1R).

2.      In Figure 1, authors mention that activation of nuclear AT1R would generate an increase in intracellular superoxide. However, symbol of superoxide in Figure 1 is not correct. Please correct the symbol.

3.      Nuclear Mas-R is not shown in Figure 1.

4.      Authors have explained the roles of tri-therapy in clinical trials and are suggesting the combinatorial therapy with ARBs. Authors should include a separate section explaining the use and importance of ARBs in clinical trials.

Author Response

Greetings, please see the attachment for our responses.  We are thankful for your comments and suggestions

Author Response File: Author Response.pdf

Reviewer 3 Report

The presented manuscript is an interesting review focused on some cardioprotective mechanisms against reperfusion injury in acute myocardial infarction. The literature data on this subject are discussed and the authors also present the possible effect of the association of three substances with demonstrated antioxidant activity - ascorbic acid, N-acetylcysteine and deferoxamine in therapy, which could contribute to the reducing of the reperfusion injury.

 In order to improve the manuscript, I have some recommendations and observations:

-        regarding the form, some titles and subtitles are preceded by a line “-“ and I didn't understand what it meant (e.g. 2.-. iRAS)

-         cap. 3. Chemically, Vitamine C is ascorbic acid, not ascorbate, so it is not correct to consider ascorbate and vitamine C as synonyms

-        In the chapter Discussion – some paragraphs refers to the results obtained by Rodrigo et al., but the corresponding reference is not mentioned. I think it’s about the reference 41

-        In fig.  2 – the legend – it is mentiond Table 1 – which is not presented.  Also I think that the abbreviation for “type 1 angiotensin II receptor” is AT1R instead of R

References 41 and 47 are the same!

Author Response

Greetings, please see the attachment for our responses.  We are thankful for your recommendations and observations

Author Response File: Author Response.pdf

Reviewer 4 Report

The manuscript by Méndez-Valdés and co-workers addresses an interesting and pertinent topic, since it is relevant to improve currently available therapeutic approaches to reperfusion injury following acute myocardial infarction. Despite its current flaws, which I detail below, I believe that this paper fits the scope of Biomedicines and that it could be considered for publication, once the following concerns are met.

 ·      I recommend that the manuscript is revised for formatting, since some aspects have not been accurately adapted to the Microsoft Word template of Biomedicines (e.g., the way that sections are sub-sections are numbered and formatted).

·      According to the instructions for authors, acronyms/abbreviations/initialisms should be defined the first time they appear in each of three sections: the abstract; the main text; the first figure or table. When defined for the first time, the acronym/abbreviation/initialism should be added in parentheses after the written-out form. Please make sure this is done for all acronyms/abbreviations/initialisms (e.g., RAS, PKC, NF-kB, IP3-R, TGF-beta, ETC, HIF, etc.).

·      Since the current manuscript is described as a review article, the authors should avoid their sometimes opinionated and biased tone in the “Discussion” section. I suggest that this section is rephrased in order to convey the same information in a more neutral way.

Author Response

Greetings, please see the attachment for our responses.  We are thankful for your comments 

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report 

Thanks a lot to the authors for providing necessary changes.