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The authors addressed reviewers comments. Considering that the last reviewer's comments impact the form, but not the background of the manuscript I decided as a academic editor accept the manuscript.
[# PeerJ Staff Note - this decision was reviewed and approved by Vladimir Uversky, a PeerJ Section Editor covering this Section #]
A minor revision is needed before acceptance. Please include the changes asked by reviewer 3. Then, submit the corrected version. When these changes are included in a new version, the manuscript can be accepted. Please submit the new version as soon as possible.
There is nothing to comment on.
There is nothing to comment on.
There is nothing to comment on.
The authors have made considerable improvements to their manuscript following the comments of reviewers. For this reviewer, the work meets the PeerJ standards and can be accepted for publication.
The authors' skillful integration of the suggested corrections has notably improved the clarity and comprehension of both the manuscripts and the accompanying data. These revisions not only enhance the overall quality of the material but also offer valuable insights into a novel murine model of hypertensive heart disease in elderly women. Such insights hold significant implications for researchers and clinicians, contributing to a deeper understanding and potentially informing the development of advanced diagnostic and therapeutic approaches in the domain of hypertensive heart disease among elderly women
Authors addressed reviewers comments
Authors addressed reviewers comments
Authors addressed reviewers comments
- Abstract section: HFpEF is not define.
- Introduction section: "nitric oxide (NO)" is not defined in the first sentence, while in the second one sentence should be written as "NO" : Lines 63-64: “Clinical trials of agents treating impaired NO signalling have been negative [13]. Thus, the role of inflammation and reduced nitric oxide bioavailability, although likely in the development of HFpEF, remains unclear.”
Authors improve clarity and quality of general scheme in Figure 1 and well describe "Schematic representation of the design of the animal study" but it is still not clear the number of animals they employed for each group of study.
The manuscript is clearly written in professional language and authors made corrections suggested before and findings about their model are well described with a clear and relevant emphasis on both the social and medical significance.
The manuscript needs improvement. It is relevant to asses all reviewer suggestions. We are happy to analyze a new version of your manuscript, considering the relevance of the information mentioned and the need for new animal models for hypertension.
**PeerJ Staff Note:** Please ensure that all review, editorial, and staff comments are addressed in a response letter and that any edits or clarifications mentioned in the letter are also inserted into the revised manuscript where appropriate.
Heart failure with preserved ejection fraction (HFpEF) includes several classical factors related to the development of this global health problem. One of them, hypertension, is the most critical risk factor for early death worldwide, also known as the risk of developing brain and kidney diseases. Hypertension per se accounts for about half of all heart disease-related deaths worldwide. There are also sex-specific differences in cardiovascular risk factors and implications for cardiovascular disease development in women. Traditional heart risk factors, including diabetes, hypertension, obesity, and smoking, have different relative risks for men and women. In addition, women are more likely to experience cardiovascular disease at any point in their lives due to a few female-specific risk factors, such as the age at which menarche and menopause occur, polycystic ovary syndrome, infertility (including ART use), parity, adverse pregnancy outcomes, spontaneous pregnancy loss, and other female-predominant conditions like migraines, depression, and autoimmune diseases. These factors are generally considered an elevated cardiovascular risk for women, who may benefit from more intense preventive interventions, including pharmacotherapy. Thus, the study and control of these factors are of great importance for public health and medicine.
It has been established that in the case of HFpEF, not only signs of heart failure but also evidence of preserved LVEF and diastolic dysfunction are required for diagnosis. The basis of consensus diagnosis includes a detailed clinical evaluation, electrocardiogram, laboratory tests, and echocardiogram. In this regard, the development of suitable HFpEF animal models reflecting these risk factors and diagnosis parameters, along with differentiation for females, is very important. In recent years, the etiology and outcome of HFpEF in animals have been intensively studied, and differentiation models have been established.
In this study, the authors analyzed the effects of a continuous infusion of angiotensin II in young and older female mice, the effects of ovariectomy in mice on heart morphology and function in aging females, and the impact of hypertensive stress in those animals. The goal was to identify the influence of gonadal steroids on the heart’s response to hypertensive stress. They observed concentric hypertrophy, preserved EF, diastolic alterations, mostly left atrial dilation, and hypertrophy in older animals. They also identified several new genes associated with cardiac aging and the reaction to hypertension in older female mice.
Besides the limitations of the study, the results of the presented work emphasize both the medical and social significance of this problem and the usefulness of the proposed model. The authors describe all the results of their work in great detail and in a highly scientific style. The submitted work meets the requirements and can be accepted for publication.
no comment
The manuscript under review presents an innovative report on a new mouse model of cardiac hypertensive disease for which the following old age, timing of gonadectomy, and AngII infusion at different stages of life while provided new evidence on left ventricle gene expression under different conditions.
1. Grammer- major revisions. Please consider sending the manuscript for English scientific editor. The writing needs to be reevaluated to make clearer and less cumbersome.
2. Introduction will benefit from explaining the mechanism that obesity and diabetes induces HFpEF (line 33)
nicely outlined primary research within Aims and Scope of the journal, the Research question is well defined (line 72-75), data presented answered the authors specific hypothesis and had significant predictive benefit which is both relevant & meaningful.
3. Methods- Line 84 experimental design is not clear.
Despite the scheme in Fig1 the experimental design is hard to understand, please simplify to make concise. Consider making an illustrated experimental design figure to highlight what are the different groups tested.
4. Results- Line 184- would change the title to the conclusion of each figure, not use lose terms as "response varies"-what is the take home message?
5. Breakdown line 184-223 into smaller sections to have clearer point across (see annotated text)
ie: Line 202 "Angiotensin II infusion resulted, cardiac hypertrophy". Line 217 "AngII caused left atrial hypertrophy"
6. Fig 4- state on the figure itself what red/orange dots represent
7. Discussion- Line 330 add hypothesis on how the genes you have found might the effect the heart tissue, add a suggested mechanism.
Limitations of the study and conclusions are well stated, linked to original research question and well supported with literature.
In the abstract section the correct name of the gene is "Arntl" instead of "Anrtl".
According to PeerJ standards, Subheadings must be bold, followed by a period, and start a new paragraph.
Authors used a clear, professional English language in the whole document. They showed an introduction with a concise background to explain the context.
The paper present relevant literature and it is well referenced, however, authors should be attend the following points:
Lines 40-41. Please add a reference for “Old age, hypertension, atrial fibrillation, and the female sex are classical factors for the development of HFpEF”.
Please check reference format: Line 42 … “and high levels of natriuretic peptides (7).” It should be square brackets.
Please check reference format: Lines 332-333, as increased (36). Ablation of Arntl in mice was associated with a protective role in the development of cardiac hypertrophy (38-42). It should be square brackets.
Figures are relevant, high quality, well labeled and described, except Figure 1. “Schematic representation of the design of the animal study”, please add a brief description after the title.
Lines 142-143, “expressed in pixels was then converted to µm2 by multiplying the number of pixels for one cardiomyocyte by the size in µm2 of a single pixel. “ please check the correct expression of “µm2”.
Line 326: "It may impair its adaptation to an insult." This idea requires more details or clarity
Figure 4, align the figures in part "C" with A and B.
Figure 5, align section "A" in the upper left corner since sections "B" and "C" are aligned to the left side except for "A".
Authors provide a description of experimental groups, however, the total number of mice in each experimental group should be declared.
Authors describe in abstract seccion "Many of these upregulated genes were shared between the ventricle and the atrium as well as in control and Ovx animals, namely for the most expressed Ankrd1, Col3a1, Col1a1, Ctgf Col8a1, and Cilp." but this information is not included in other sections of the paper. These findings should be described in results and discussion.
The article presents relevant information, nevertheless, the conclusion lacks remarkable information. Please, restructuring the conclusion considering the main aspects or findings of their research as well as the relevance of their contribution and open the door to future research.
I commend the authors for their extensive data set. In addition, the manuscript is clearly written in professional language. Nevertheless, there is a series of points mentioned above which should be improved.
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