Sphingolipids in Atherosclerosis: Chimeras in Structure and Function

Round 1

Reviewer 1 Report

The review addresses an important topic in clinical medicine and is very well described. Therefore, I made considerations so that the authors can think about it and seek to improve the study.

1- Please add a reference in the second paragraph of the introduction.

2- “Atherosclerotic cardiovascular disease is a progressive and lifestyle dependent condition characterized by arterial lesions that initiate vasoconstriction, reduced and/or turbulent blood flow, hemostasis, and inflammation.” Oxidative stress would not play an important role in the progression of atherosclerosis.

3- In the development of atherosclerosis in addition to the formation of atheromatous plaque by the processes described in the review, does the vessel undergo adverse remodeling?

4- 3.1 NO production: “Cer has been implicated as an important regulator of endothelial NO production, as a C2 ceramide-dependent increase of superoxide anion causes endothelium-dependent vasorelaxation in small bovine coronary arteries [87], and possibly also elevates NO production. This notion is further supported by the finding that ceramide reduces the release of NO from human umbilical vein endothelial cells [93, 94] and initiates the production of superoxide anion [95-97]. In conclusion, ceramide can promote endothelial dysfunction by decreasing NO due to increased ROS concentrations, thus promoting the development of atherosclerosis”. This paragraph got confusing. Does Cer increase NO or superoxide anion production, improve endothelial function, or lead to endothelial dysfunction?

Author Response

Please see the attachment

Reviewer 2 Report

 

 

The aim of this Review is to clear up the mechanisms of atherosclerosis progression and prevention. The Authors focuses on the role of various classes of sphingolipids. The main analytical finding uncovers controversial properties of sphingolipids, including atheroprotective and atheropromoting effects.

 This is very important and interesting Review providing new insights on the problem of atherosclerosis prevention and treatment. It definitely can be published in IJMS

 

There are only several small recommendations:

 

1.If it is possible, please, improve Abstract.

It would be good to make first phrases more hooking.  And … please, underline the most important analytical findings of the Review.

2. Some places are too wordy and are difficult to read.

If it is possible, please, split for subsections Chapter 2 (Dihydroceramide in atherosclerosis progression), and please, make more subsections in Chapter 3 (Ceramide)

3. Please, concentrate Conclusion by focusing it on the main insights and new findings of the Review.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf