{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:14:57Z","timestamp":1791224097928,"version":"4.1.0"},"reference-count":93,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T00:00:00Z","timestamp":1743033600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Health Science Reports"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Atherosclerosis is the leading cause of cardiovascular disease (CVD). Historically, the management of atherosclerosis was focused on decreasing lipid profile levels; however, recent evidence demonstrated that platelets and leukocytes play an important role in forming and exacerbating atherosclerosis. L\u2010arginine (L\u2010Arg), a precursor to nitric oxide (NO), plays a critical role in modulating oxidative stress and influencing platelet\u2010leukocyte recruitment and has been extensively addressed in the context of CVD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>We aimed to perform a comprehensive literature review on <jats:sc>L<\/jats:sc>\u2010Arg metabolism in the causative pathway of atherosclerosis compared to conventional treatment and it as a putative therapeutic approach.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>L\u2010Arg supplementation has shown promising effects on NO production, improving endothelial function and reducing oxidative stress in preclinical models. Clinical studies have indicated moderate improvements in vascular health markers, including reductions in inflammation and oxidative stress, although results have varied across studies. The potential of <jats:sc>L<\/jats:sc>\u2010Arg to modify platelet\u2010leukocyte recruitment and slow the progression of atherosclerotic plaque development has been observed in certain studies. However, these benefits remain inconsistent, and more robust clinical trials are needed to confirm its effectiveness. Additionally, while <jats:sc>L<\/jats:sc>\u2010Arg appears to be relatively safe, some studies reported mild gastrointestinal discomfort as a common side effect.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:sc>L<\/jats:sc>\u2010Arg holds potential as a complementary or alternative treatment for atherosclerosis, particularly in improving endothelial function and reducing inflammation and oxidative stress. However, the variability in clinical outcomes and the lack of long\u2010term data required further investigation into assessing therapeutic benefits. Future studies should focus on determining optimal dosing regimens, evaluating their long\u2010term safety, and assessing their potential in combination with other therapies to enhance cardiovascular outcomes.<\/jats:p><\/jats:sec>","DOI":"10.1002\/hsr2.70544","type":"journal-article","created":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T13:33:33Z","timestamp":1743341613000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Is L\u2010Arginine an Appropriate Alternative for Conventional Anti\u2010Atherosclerotic Therapy?: A Comprehensive Review"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7217-3264","authenticated-orcid":false,"given":"Ali","family":"Mortezaei","sequence":"first","affiliation":[{"name":"Student Research Committee Gonabad University of Medical Sciences Gonabad Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Ghorbani","sequence":"additional","affiliation":[{"name":"Faculty of Allied Medicine, Department of Medical Laboratory Sciences Gonabad University of Medical Sciences Gonabad Iran"},{"name":"Department of Hematology and Blood Banking, School of Allied Medical Sciences Shahid Beheshti University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bardia","family":"Hajikarimloo","sequence":"additional","affiliation":[{"name":"School of Medicine Shahid Beheshti University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Sameer","sequence":"additional","affiliation":[{"name":"College of Medicine University of Sharjah Sharjah UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toba","family":"Kazemi","sequence":"additional","affiliation":[{"name":"Cardiovascular Diseases Research Center Birjand University of Medical Sciences Birjand Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ebrahim","family":"Salavati","sequence":"additional","affiliation":[{"name":"Allameh Bohlool Hospital Gonabad University of Medical Sciences Gonabad Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3658-1551","authenticated-orcid":false,"given":"Mohsen","family":"Hamidpour","sequence":"additional","affiliation":[{"name":"HSC Research Center, Department of Hematology and Blood Banking, School of Allied Medical Sciences Shahid Beheshti University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Esmail","family":"Gheydari","sequence":"additional","affiliation":[{"name":"Department of Cardiology, School of Medicine, Taleghani Hospital Shahid Beheshti University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,27]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000757"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehab892"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.7692"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.118.311572"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOL.0000000000000330"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehx144"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00150.2016"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2013.07.004"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines8080277"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1707914"},{"key":"e_1_2_13_12_1","doi-asserted-by":"crossref","unstructured":"Q.Tong X.Yang S. R.Ma X. F.Zhang Y.Wang andJ. D.Jiang 2020. Hydroxyurea Regressed Atherosclerosis Plaques in ApoE\u2010\/\u2010Mice: A Discovery Based on Clinic.","DOI":"10.21203\/rs.3.rs-32322\/v1"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep33657"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.13.2.197"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1990440"},{"issue":"1","key":"e_1_2_13_16_1","first-page":"81","article-title":"History, Progress and Future Challenges of Artificial Blood Vessels: A Narrative Review","volume":"3","author":"Hu K.","year":"2022","journal-title":"Biomater Transl"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.5101\/nbe.v14i4.p329-342"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000110785.96039.f6"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2013.01.006"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.103.25.3099"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000015853.59427.32"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00047.2009"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.medidd.2024.100189"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.2c11058"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.3402\/jev.v4.27066"},{"issue":"2","key":"e_1_2_13_26_1","first-page":"655","article-title":"Regulation of Protein Expression by L\u2010Arginine in Endothelial Cells","volume":"3","author":"Lei X.","year":"2011","journal-title":"Frontiers in Bioscience (Scholar Edition)"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2008.11.203"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222011170"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.24.10043"},{"key":"e_1_2_13_30_1","doi-asserted-by":"crossref","unstructured":"C. J.Forsyth M. R.Adams W.Jessup J.Robinson andD. S.Celermajer 1995\u201cOral L\u2010Arginine Inhibits Platelet Aggregation but Does not Enhance Endothelium\u2010Dependent Dilation in Healthy Young Men\u201dJournal of the American College of Cardiology26 no. 4 (1995): 1054\u20131061 https:\/\/elibrary.cclhd.health.nsw.gov.au\/cclhdjspui\/handle\/1\/1367.","DOI":"10.1016\/0735-1097(95)00257-9"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2020.12.009"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10082111"},{"key":"e_1_2_13_33_1","doi-asserted-by":"crossref","unstructured":"A.Sacchi G.Grassi V.Bordoni et al. \u201cEarly Expansion of Myeloid\u2010Derived Suppressor Cells Inhibits SARS\u2010CoV\u20102 Specific T\u2010Cell Response and May Predict Fatal COVID\u201019 Outcome \u201dCell Death & Disease 11 no. 921 (2020) https:\/\/www.nature.com\/articles\/s41419-020-03125-1.","DOI":"10.1038\/s41419-020-03125-1"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2156"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines9091214"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-11-010389"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0803523"},{"issue":"1","key":"e_1_2_13_38_1","first-page":"63","article-title":"L\u2010Arginine Inhibits Neutrophil Adherence and Coronary Artery Dysfunction","volume":"31","author":"Sato H.","year":"1996","journal-title":"Cardiovascular Research"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.95.3.662"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9092772"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2020.02.024"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.114.303312"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2014.6221"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2023.108441"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/7843685"},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.117.310042"},{"key":"e_1_2_13_47_1","doi-asserted-by":"publisher","DOI":"10.3349\/ymj.2018.59.3.366"},{"key":"e_1_2_13_48_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.15.6.704"},{"key":"e_1_2_13_49_1","doi-asserted-by":"publisher","DOI":"10.1161\/hy0202.103473"},{"key":"e_1_2_13_50_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.683656"},{"key":"e_1_2_13_51_1","doi-asserted-by":"publisher","DOI":"10.1159\/000111332"},{"key":"e_1_2_13_52_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.2002.2082"},{"key":"e_1_2_13_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-019-0262-y"},{"key":"e_1_2_13_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-50753-8"},{"key":"e_1_2_13_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-017-2727-4"},{"key":"e_1_2_13_56_1","doi-asserted-by":"publisher","DOI":"10.1080\/10408363.2016.1200008"},{"key":"e_1_2_13_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/hsr2.70209"},{"issue":"7","key":"e_1_2_13_58_1","first-page":"454","article-title":"Mac\u20101 Alongside Platelet\u2010Monocyte Aggregates as Potential Markers in Acute Coronary Syndrome: A Case\u2010Control Study","volume":"26","author":"Shahraki H.","year":"2024","journal-title":"Cell Journal (Yakhteh)"},{"key":"e_1_2_13_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2017.51"},{"key":"e_1_2_13_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.12.022"},{"key":"e_1_2_13_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2005.02.054"},{"key":"e_1_2_13_62_1","doi-asserted-by":"publisher","DOI":"10.1111\/eci.12228"},{"key":"e_1_2_13_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2019.06.919"},{"key":"e_1_2_13_64_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa8064"},{"key":"e_1_2_13_65_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.120.315931"},{"key":"e_1_2_13_66_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehp330"},{"key":"e_1_2_13_67_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11233843"},{"key":"e_1_2_13_68_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11883-017-0678-6"},{"key":"e_1_2_13_69_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi701677r"},{"key":"e_1_2_13_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2019.11.004"},{"key":"e_1_2_13_71_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4133"},{"key":"e_1_2_13_72_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201300033"},{"key":"e_1_2_13_73_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.1c08391"},{"key":"e_1_2_13_74_1","doi-asserted-by":"publisher","DOI":"10.1134\/S0006297916110134"},{"key":"e_1_2_13_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2015.04.003"},{"key":"e_1_2_13_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2023.106702"},{"key":"e_1_2_13_77_1","doi-asserted-by":"publisher","DOI":"10.3109\/08860221003592820"},{"key":"e_1_2_13_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2011.03.025"},{"key":"e_1_2_13_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2021.109568"},{"key":"e_1_2_13_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2022.07.004"},{"key":"e_1_2_13_81_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-020-00312-6"},{"key":"e_1_2_13_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tice.2023.102036"},{"key":"e_1_2_13_83_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26226949"},{"key":"e_1_2_13_84_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu11071679"},{"key":"e_1_2_13_85_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jnatprod.1c01141"},{"key":"e_1_2_13_86_1","doi-asserted-by":"publisher","DOI":"10.3390\/foods12101937"},{"issue":"20","key":"e_1_2_13_87_1","first-page":"6991","article-title":"HOTAIR Alleviates Ox\u2010LDL\u2010Induced Inflammatory Response in Raw264. 7 Cells via Inhibiting NF\u2010\u03baB Pathway","volume":"22","author":"Pang J. L.","year":"2018","journal-title":"European Review for Medical and Pharmacological Sciences"},{"key":"e_1_2_13_88_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612826666200318152049"},{"key":"e_1_2_13_89_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2014.02.012"},{"key":"e_1_2_13_90_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22052719"},{"key":"e_1_2_13_91_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2020.103567"},{"key":"e_1_2_13_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rvsc.2022.06.022"},{"key":"e_1_2_13_93_1","doi-asserted-by":"publisher","DOI":"10.4274\/balkanmedj.2017.0246"},{"key":"e_1_2_13_94_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nutres.2020.03.003"}],"container-title":["Health Science Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hsr2.70544","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T02:24:55Z","timestamp":1746411895000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/hsr2.70544"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,27]]},"references-count":93,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1002\/hsr2.70544"],"URL":"https:\/\/doi.org\/10.1002\/hsr2.70544","archive":["Portico"],"relation":{},"ISSN":["2398-8835","2398-8835"],"issn-type":[{"value":"2398-8835","type":"print"},{"value":"2398-8835","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,27]]},"assertion":[{"value":"2024-09-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70544"}}