Emerging Roles of Cardiotrophin-1 in the Pathogenesis and Biomarker of Atherosclerosis

Round 1

Reviewer 1 Report

An excellent and concise review paper that merits publication as it is.

Author Response

Thank you very much.

Reviewer 2 Report

Study Summary

The study highlighted the role of cardiotrophin 1 in the pathophysiology of atherosclerosis and as a possible biomarker for cardiovascular disease and metabolic disease. The review is well written, tables and figures are clear and relevant.

      Major

Page-2 section- 4 Receptor and signaling of CT-1. This section need to be expanded to include the biological outcomes for each of the pathways that listed to be activated by CT-1. Are any of the downstream biological response via the mentioned induced pathways have an effect on atherosclerosis or cardio disease? This needs to be stated and clearly discussed.  

Page 2 section2, 3 and 5. These sections have to either be combined into one section that generally explained CT-1 (Structure, expression and function) or expanded with more details in a way that worth having each as separate section.

Page -5 Table -1 all values should have the same unit for easier comparison. Please make sure that all values in the table have same unit e.g. PM. 

Page -4 figure-1. The figure illustrates the cellular and molecular mechanisms of CT-1 effects on Inflammation, foam cell formation and migration& production. Figure caption should be expanded to include the references that demonstrated the effect of CT-1 on each of the followings: Inflammation, foam cell formation and migration& production.

Minor

Please cite the followings:  line (11,13,15,16,19,21,23,31,35,37).

Line 92 should read "CT-1 has regulatory effects on glucose...." - consider sentence reconstruction.

Line 100 should read “Plasma CT-1 concentration further increases in the presence........"

Line 223 should read “CT-1 is known to be a mediator capable of hypertension induced.........."

Line 224 sentence reconstruction necessary.

Out of the 92 references, only 27 are within 5 years (dating back to 2013). However most of the references are within the last 10 years (dating back to 2008). More recent references are needed

Author Response

I am very grateful to the reviewer for careful and constructive comments that have been helpful in improving significantly the manuscript. 

Major:

1. We have provided the Figure regarding the signal transductions in a variety of cardiovascular responses (Revised Figure 1).

2. Sections 2, 3, and 5 have been combined and the header has been corrected to “Structure, Expression, and Function of CT-1.” 

3. The unit has been unified to pM (Table 1).

4. CT-1 stimulates endothelial and monocyte inflammation [26,61,62,64–66], macrophage foam cell formation [15], and the migration and proliferation of VSMCs [15] (Revised Figure 3 legend). 

Minor:

1. The references have been provided excepting in the abstract.

2. As indicated, the sentence has been corrected (L.82-84).

3. As indicated, the sentence has been corrected (L.125).

4. As indicated, the sentence has been corrected (L.266).

5. As indicated, the sentence has been corrected (L.267-268).

6. Several recent references have been added (Ref.3,57).