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Review
Peer-Review Record

Programming of Vascular Dysfunction in the Intrauterine Milieu of Diabetic Pregnancies

Int. J. Mol. Sci. 2018, 19(11), 3665; https://doi.org/10.3390/ijms19113665
by Nada A. Sallam 1,2,3, Victoria A. C. Palmgren 1, Radha D. Singh 1,2, Cini M. John 1 and Jennifer A. Thompson 1,2,*
Reviewer 1: Anonymous
Reviewer 2: Anonymous
Int. J. Mol. Sci. 2018, 19(11), 3665; https://doi.org/10.3390/ijms19113665
Submission received: 24 October 2018 / Revised: 14 November 2018 / Accepted: 16 November 2018 / Published: 20 November 2018
(This article belongs to the Special Issue Risk Factors and Molecular Mechanisms of Gestational Diabetes)

Round  1

Reviewer 1 Report

The manuscript is overall well written.

I just have some minor concerns:

- The Authors should expand the section on epigenetics, discussing the following topics (recently reviewed in J Cell Physiol. 2016 Aug;231(8):1638-44):

differentially expressed miRs were identified in the blood and in exosomes isolated from serum of healthy controls compared with patients with metabolic syndrome, type 2 diabetes, hypercholesterolemia or hypertension

a significant increase in circulating miR-126 has been detected in patients with acute myocardial infarction and angina whereas miR-126 downregulation has been reported in plasma from patients with diabetes, heart failure, or cancer.

- It is advisable to the Authors to incorporate a pictorial or cartoon representation of the proposed mechanisms in order to facilitate the comprehension and increase the overall impact of the manuscript.


Author Response

-The Authors should expand the section on epigenetics, discussing the following topics (recently reviewed in J Cell Physiol. 2016 Aug;231(8):1638-44):

Response: Thank you. We have added a paragraph focused on miRNA. In this section, we have highlighted that miRNAs are involved in the pathogenesis of several diseases and have described a few studies identifying a role for specific miRNAs in vascular disease/dysfunction. We also point to the study described in the preceding paragraph, wherein miR-101 was found to be involved in the dysregulation of HUVEC from GDM pregnancies. 

-It is advisable to the Authors to incorporate a pictorial or cartoon representation of the proposed mechanisms in order to facilitate the comprehension and increase the overall impact of the manuscript

Response: Thank you. We very much agree and have added a figure to summarize the proposed mechanisms linking GDM to later-life vascular dysfunction in the offspring.


Reviewer 2 Report

To the authors

In this manuscript, the authors reviewed the association between maternal GDM and the offspring’s vascular function. This manuscript was well-written and summarized current findings. A few minor revisions are listed below. 

1.The authors discussed the relationship between intrauterine environment and later-life vascular function. However, it is difficult for me to understand what effects occurred at birth and what did in adulthood. I am slightly confused. The authors should clearly organize what happened soon after birth and what happened after growth. 

2.The authors mentioned high circulating leptin in GDM mothers. I think that it is useful to discuss the role of maternal leptin on the offspring’s vascular function mentioned in Pennington’ paper (PLoS One. 2016; 11: e0155377).

3.In line 50, “systemic” should read systematic.

4.In line 58-59, appropriate citations are required. 

5.In line 88-89, appropriate citations are required. 

6.In line 132-133, appropriate citations are required. 

7.In line 137, is the subhead “Vascular reactivity” necessary? 


Author Response

1. The authors discussed the relationship between intrauterine environment and later-life vascular function. However, it is difficult for me to understand what effects occurred at birth and what did in adulthood. I am slightly confused. The authors should clearly organize what happened soon after birth and what happened after growth. 

Response: Thank you. We have modified our table to clearly differentiate the changes that have been observed at the following stages: birth, newborn, childhood/adolescence. 

2. The authors mentioned high circulating leptin in GDM mothers. I think that it is useful to discuss the role of maternal leptin on the offspring’s vascular function mentioned in Pennington’ paper (PLoS One. 2016; 11: e0155377).

Response: We have included a discussion of this model and of the findings reported by the Pennington paper.

3. In line 50, “systemic” should read systematic.

Response: this was edited

4.In line 58-59, appropriate citations are required. 

Response: citations were added

5.In line 88-89, appropriate citations are required. 

Response: citations were added

6.In line 132-133, appropriate citations are required. 

Response: citations were added

7.In line 137, is the subhead “Vascular reactivity” necessary? 

Response: this subheading was removed



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