Perivascular Adipose Tissue Inflammation: The Anti-Inflammatory Role of Ghrelin in Atherosclerosis Progression

Round 1

Reviewer 1 Report

The review is very well written, and is definitely recommended for publication. The only addition I would recommend is a basic description of the molecular structure and properties of ghrelin - primary structure, functional regions, etc.   

Author Response

No revision was required.

Reviewer 2 Report

The manuscript titled “Perivascular adipose tissue inflammation: the anti-inflammatory role of ghrelin in atherosclerosis progression” is a mini-review that summarized the role of ghrelin in atherosclerosis protection and adipose tissue remodeling. With 11 authors’ contributions but only about 6 pages of easy-to-read context, the listed references have not been well-reviewed and summarized. Except for this, I only have a few remarks listed below for the format or editing that the authors may want to consider.

Minor Concerns and Comments:

1. Line 69: “IL 1β” should be “IL-1β”.
2. Line 70: I’d suggest the authors add references. Or the reference for this sentence is reference [7] at the end of the paragraph.
3. Line 162: “VEGF” should be defined in line 81 where it’s the first time be used.
4. Line 206: A space is missing in front of [38].
5. Line 216: A space is missing in front of [42].
6. Table 1: The authors use “NF-κB” in Table 1, while its full name is in line 70. I’d suggest the authors just use “NF-κB” in line 70.

Author Response

 

We thank the Referees for their interest in our work and for helpful comments that will greatly improve the manuscript Perivascular adipose tissue inflammation: the anti-inflammatory role of ghrelin in atherosclerosis progression.

1. We added references to justify our findings.
2. The reference at the end of the paragraph does not apply to that piece of information. The following citation has been inserted: Li WG, Gavrila D, Liu X, Wang L, Gunnlaugsson S, Stoll LL, McCormick ML, Sigmund CD, Tang C, Weintraub NL. Ghrelin inhibits proinflammatory responses and nuclear factor-κB activation in human endothelial cells. Circulation. 2004 May 11;109(18):2221-6.
3. Spelling and abbreviation suggestions being considered, the phrase “Ghrelin inhibits cytokine release (IL 1β, IL-6, and TNF-α) in endothelial cells by activating the nuclear factor kappa κB.” became “Ghrelin inhibits cytokine release (IL-1β, IL-6, and TNF-α) in endothelial cells by inhibiting the activation of NF-κB”.
4. We have made the recommended changes.

Reviewer 3 Report

This reveiw article is about ghrelin-induced anti-inflammatory 
effects on adipose tissue macrophage infiltration and the inhibitory activity of ghrelin on the proinflammatory adipokine secretion. 
The results show that the impact of ghrelin on the endothelial function should be studied to PVAT.Overall, the manuscript is fair, logical, and well written.  The references are appropriate, adequate and up to date. I recommend this article for publication.

Author Response

The following paragraph was added:

“Human ghrelin (C₁₄₉H₂₄₉N₄₇O₄₂) is the endogenous ligand for growth-hormone secretagogue receptor (GHS-R), GHS-R1a being its functional form. Ghrelin is a 28 amino acid peptide secreted by the P/D1 cells lining the stomach fundus. Human ghrelin differs from rat only in amino acids in position 11 and 12. In order to be recognized by the GHS-R1a receptor and to stimulate growth hormone release from the pituitary gland, the ghrelin’s serine at position 3 is acylated by a fatty acid, the n-octanoic acid, near its N-terminal region, before secretion. Ghrelin acylation is triggered by an enzyme known as ghrelin O-acyl transferase (GOAT) [3]. The non-modified ghrelin is called desacyl ghrelin and circulates as a free peptide, whereas acyl ghrelin is bound to lipoproteins. Plasma levels of desacyl ghrelin are about 4 or 5 times higher than those of acyl ghrelin in non-pathological states [4].”

The following references were used:

“[3] Sieburg MA, Cleverdon ER, Hougland JL. Biochemical Assays for Ghrelin Acylation and Inhibition of Ghrelin O-Acyltransferase. Methods Mol Biol. 2019;2009:227-241.

[4] Nishida T, Tsubouchi H, Hamada T, Imamura N, Hiyoshi M, Yano K, Kangawa K, Nakazato M, Nanashima A. Plasma desacyl ghrelin-to-acyl ghrelin ratio is a predictor of postoperative complications and prognosis after pancreaticoduodenectomy. Oncol Lett. 2019 Nov;18(5):4974-4983.”

Round 2

Reviewer 2 Report

For the manuscript itself, I have no further comments about this short review.