Effects of smoking cessation using varenicline on the serum concentrations of oxidized high-density lipoprotein: Comparison with high-density lipoprotein cholesterol

Akira Umeda; Kazuya Miyagawa; Atsumi Mochida; Hiroshi Takeda; Yoshiyuki Ohira; Toru Kato; Yasumasa Okada; Kazuhiko Kotani

doi:10.1371/journal.pone.0277766

Peer Review History

Original SubmissionMarch 10, 2022
9 Aug 2022 Decision Letter - Laura Calabresi, Editor PONE-D-22-07258Effects of smoking cessation using varenicline on the serum concentrations of oxidized high-density lipoprotein: Comparison with high-density lipoprotein cholesterolPLOS ONE Dear Dr. Umeda, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by Sep 23 2022 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. Please include the following items when submitting your revised manuscript: A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols. We look forward to receiving your revised manuscript. Kind regards, Laura Calabresi Academic Editor PLOS ONE Journal Requirements: When submitting your revision, we need you to address these additional requirements. 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf 2. We note that you have stated that you will provide repository information for your data at acceptance. Should your manuscript be accepted for publication, we will hold it until you provide the relevant accession numbers or DOIs necessary to access your data. If you wish to make changes to your Data Availability statement, please describe these changes in your cover letter and we will update your Data Availability statement to reflect the information you provide. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Partly Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: N/A Reviewer #2: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ****** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: In this work the authors demonstrated that smoking cessation with varenicline decreased oxHDL and increased HDL-C and the effect on oxHDL was thought to be associated with the effectiveness of smoking cessation. Even the work is well conducted, it has several limitations that have to be addressed: 1. It seems that oxHDL are positively correlated with serum levels of HDL-C. How the authors explain this correlation? It seems that subject with high level of HDL-C, potentially more protected, have also high level of dysfunctional oxHDL. Authors should discuss this point. 2. Figure 5A. Add the linear correlation in the graph will clarify the message 3. Do the authors take into account change in life-style (exercise, diet) after smoking quite in multiple regression analysis? This is an important point that can influence HDL-C concentration. 4. The study completely lack of functional assays to determine HDL functionality which are essential to support conclusions. 5. It is unclear if the correlation with oxHDL and FMD was related to a previous study, it is important add FMD evaluation also for this study. Reviewer #2: This is an interesting and well-presented article on the effects of smoking cessation with varenicline on the levels of oxHDL. I have few comments that could improve the manuscript: 1)The determination of oxHDL is performed using a monoclonal antibody against oxidized apoA-I. Is it known what type of oxidation in apoA-I is determined? 2)The role of oxidized apoA-I in atherosclerosis and cardiovascular disease should be discussed. 3)How do the authors speculate that varenicline could affect the levels of oxHDL? Is there an effect of varenicline in myeloperoxidase (MPO) mass or activity in subjects? 4)Is lipid peroxidation content of HDL also reduced following smoking sensation? 5)Introduction: “oxHDL has been used in animal models of vascular injury”. What does this mean? What was the use of ox-HDL in the particular animal model? ****** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: No Reviewer #2: No ******** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0277766.r001
Revision 1
21 Sep 2022 Author Response Dear Reviewers of PLOS ONE, Hello. Thank you very much for reviewing our paper entitled, “Effects of smoking cessation using varenicline on the serum concentrations of oxidized high-density lipoprotein: Comparison with high-density lipoprotein cholesterol”. We would like to respond to your comments as follows. Reviewer #1: (Comment) In this work the authors demonstrated that smoking cessation with varenicline decreased oxHDL and increased HDL-C and the effect on oxHDL was thought to be associated with the effectiveness of smoking cessation. Even the work is well conducted, it has several limitations that have to be addressed: 1. It seems that oxHDL are positively correlated with serum levels of HDL-C. How the authors explain this correlation? It seems that subject with high level of HDL-C, potentially more protected, have also high level of dysfunctional oxHDL. Authors should discuss this point. (Response) The definite explanations of the cross-sectional positive correlation of HDL-C to oxHDL remain unclear, but for instance, in chronic exposure to smoking, a native HDL particle may be hypothesized to act as an acceptor to the smoking-induced oxidants as a previous study presumed a removal action of HDL particles to the smoking-induced oxidants [29]. In addition, it seems that high levels of HDL-C do not always mean protecting against coronary artery disease [30]. We wrote these sentences in the middle of the 2nd paragraph of the Discussion (Line 255-61). (Comment) 2. Figure 5A. Add the linear correlation in the graph will clarify the Message (Response) We added the linear correlation in the graph in Figure 5A. (Comment) 3. Do the authors take into account change in life-style (exercise, diet) after smoking quite in multiple regression analysis? This is an important point that can influence HDL-C concentration. (Response) Although we did not take into account changes in lifestyle (exercise, diet) after smoking quit in this multiple regression analysis, consideration of this lifestyle change factor may be important for future studies. (We wrote this in the last of the 6th paragraph in the Discussion. Line 297-9) (Comment) 4. The study completely lack of functional assays to determine HDL functionality which are essential to support conclusions. (Response) The oxidized HDL has been reported to appear in pathophysiologic conditions with dysfunction of HDL, assuming that oxHDL can be a measure of dysfunctional HDL [11, 17, 34, 35]. Thus, oxHDL can be a risk marker for atherosclerosis and cardiovascular disease. We wrote these sentences in the 7th paragraph of the Discussion (Line 307-10). (Comment) 5. It is unclear if the correlation with oxHDL and FMD was related to a previous study, it is important add FMD evaluation also for this study. (Response) There was no significant association between baseline oxHDL and baseline FMD, as well as between ΔoxHDL and ΔFMD. Although both oxHDL and FMD have been reported to associate with atherosclerosis, these two factors might not be linked. (We wrote this in the 7th paragraph of the Discussion. Line 305-7) Reviewer #2: (Comment) This is an interesting and well-presented article on the effects of smoking cessation with varenicline on the levels of oxHDL. I have few comments that could improve the manuscript: 1)The determination of oxHDL is performed using a monoclonal antibody against oxidized apoA-I. Is it known what type of oxidation in apoA-I is determined? (Response) Originally, the assay of oxHDL used in the study was based on the H2O2-induced oxidative modification of apoA-I [11]. We wrote this in the “Measurement of oxHDL and HDL-C” paragraph of Methods (Line 134-5). (Comment) 2)The role of oxidized apoA-I in atherosclerosis and cardiovascular disease should be discussed. (Response) The oxidized HDL has been reported to appear in pathophysiologic conditions with dysfunction of HDL, assuming that oxHDL can be a measure of dysfunctional HDL [11, 17, 34, 35]. Thus, oxHDL can be a risk marker for atherosclerosis and cardiovascular disease. We wrote these sentences in the last of the 7th paragraph of the Discussion (Line 307-10). (Comment) 3)How do the authors speculate that varenicline could affect the levels of oxHDL? Is there an effect of varenicline in myeloperoxidase (MPO) mass or activity in subjects? (Response) Experimental studies report that varenicline itself affected oxidative stress in rats [40, 41]. According to their “chronic” experiments, varenicline significantly decreased antioxidants of superoxide dismutase, catalase, glutathione, and glutathione peroxidase levels, and increased oxidant levels comprising malondialdehyde and myeloperoxidase. Oguz et al. reported that the “acute” usage of varenicline (mimicking the human use for smoking cessation) significantly decreased rats’ superoxide dismutase in kidney and testis tissues [40]. From our study, the reduction of oxidation to HDL via smoking cessation is wholly thought to be superior to the increased tendency to oxidation by varenicline itself. We wrote these sentences in the last paragraph of the Discussion (Line 321-9). (Comment) 4)Is lipid peroxidation content of HDL also reduced following smoking sensation? (Response) Smoking induces oxidation of proteins and lipids [42, 43], and oxHDL stems from oxidative modification of HDL (containing apoA-I). Thus, the current study suggests that the peroxidation content of HDL is also reduced following smoking cessation with the use of varenicline. Together, smoking cessation without the help of varenicline might be better for vascular health. We wrote these sentences in the last paragraph of the Discussion (Line 329-33). (Comment) 5)Introduction: “oxHDL has been used in animal models of vascular injury”. What does this mean? What was the use of ox-HDL in the particular animal model? (Response) He et al. demonstrated that apoA-I mimetic peptide 4F inhibited oxHDL-induced dysfunction of endothelial repairing in a mice model of vascular electric injury [19]. We wrote this in the last of the second paragraph in the Introduction (Line 79-81). Changed portions are indicated in red. We made some tiny corrections using the software “Grammarly”. We consistently used the abbreviation of apolipoprotein A-1 (apoA-I). (Line 71 and throughout the paper) Fig. 6. Row 1 column 5. “R between before data” was changed to “R between baseline data”. We hope you will feel our paper interesting and accept it for publication. Sincerely, 21 Sep 2022 Akira Umeda, M.D., Ph.D. Attachments Attachment Submitted filename: Response to Reviewer.docx https://doi.org/10.1371/journal.pone.0277766.r002
3 Nov 2022 Decision Letter - Donovan Anthony McGrowder, Editor Effects of smoking cessation using varenicline on the serum concentrations of oxidized high-density lipoprotein: Comparison with high-density lipoprotein cholesterol PONE-D-22-07258R1 Dear Dr. Umeda, We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Donovan Anthony McGrowder, PhD., MA., MSc Academic Editor PLOS ONE Additional Editor Comments: Dear Dr. Umeda, The manuscript entitled “Effects of smoking cessation using varenicline on the serum concentrations of oxidized high-density lipoprotein: Comparison with high-density lipoprotein cholesterol” was revised in accordance with the reviewers’ comments and is provisionally accepted pending final checks for formatting and technical requirements. Regards, Dr. Donovan McGrowder (Academic Editor) https://doi.org/10.1371/journal.pone.0277766.r003
Formally Accepted
18 Nov 2022 Acceptance Letter - Donovan Anthony McGrowder, Editor PONE-D-22-07258R1 Effects of smoking cessation using varenicline on the serum concentrations of oxidized high-density lipoprotein: Comparison with high-density lipoprotein cholesterol Dear Dr. Umeda: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Donovan Anthony McGrowder Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0277766.r004

Open letter on the publication of peer review reports

PLOS recognizes the benefits of transparency in the peer review process. Therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. Reviewers remain anonymous, unless they choose to reveal their names.

We encourage other journals to join us in this initiative. We hope that our action inspires the community, including researchers, research funders, and research institutions, to recognize the benefits of published peer review reports for all parts of the research system.

Learn more at ASAPbio .