{"id":"https://openalex.org/W7225808400","doi":"https://doi.org/10.20944/preprints202611.1108.v1","title":"Porphyromonas gingivalis-Derived LPS Disrupts BH4\u2013eNOS Signaling in Primary Human Umbilical Vein Endothelial Cells: Modulation by Sepiapterin and CDDO-Me","display_name":"Porphyromonas gingivalis-Derived LPS Disrupts BH4\u2013eNOS Signaling in Primary Human Umbilical Vein Endothelial Cells: Modulation by Sepiapterin and CDDO-Me","publication_year":2026,"publication_date":"2026-11-11","ids":{"openalex":"https://openalex.org/W7225808400","doi":"https://doi.org/10.20944/preprints202611.1108.v1"},"language":"en","primary_location":{"id":"doi:10.20944/preprints202611.1108.v1","doi":"https://doi.org/10.20944/preprints202611.1108.v1","is_oa":true,"landing_page_url":"https://doi.org/10.20944/preprints202611.1108.v1","pdf_url":null,"source":{"id":"https://openalex.org/S6309402219","display_name":"Preprints.org","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":["https://openalex.org/P4310310987"],"host_organization_lineage_names":["Multidisciplinary Digital Publishing Institute"],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"posted-content"},"volume":null,"type":"preprint","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://doi.org/10.20944/preprints202611.1108.v1","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5161449678","display_name":"Gunaraj Dhungana","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Gunaraj Dhungana","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5010009334","display_name":"Chethan Sampath","orcid":"https://orcid.org/0000-0002-6396-227X","observed_orcids":["https://orcid.org/0000-0002-6396-227X"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Chethan Sampath","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"last","author":{"id":"https://openalex.org/A5078033952","display_name":"Pandu R. Gangula","orcid":"https://orcid.org/0000-0001-7259-570X","observed_orcids":["https://orcid.org/0000-0001-7259-570X"]},"institutions":[],"countries":[],"is_corresponding":true,"raw_author_name":"Pandu R. Gangula","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":["https://openalex.org/A5078033952"],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10155","display_name":"Nitric Oxide and Endothelin Effects","score":0.7221999764442444,"subfield":{"id":"https://openalex.org/subfields/2737","display_name":"Physiology (medical)"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10155","display_name":"Nitric Oxide and Endothelin Effects","score":0.7221999764442444,"subfield":{"id":"https://openalex.org/subfields/2737","display_name":"Physiology (medical)"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10257","display_name":"Oral microbiology and periodontitis research","score":0.2705000042915344,"subfield":{"id":"https://openalex.org/subfields/3506","display_name":"Periodontics"},"field":{"id":"https://openalex.org/fields/35","display_name":"Dentistry"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10371","display_name":"Immune Response and Inflammation","score":0.0006000000284984708,"subfield":{"id":"https://openalex.org/subfields/2403","display_name":"Immunology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[],"concepts":[{"id":"https://openalex.org/C2777411675","wikidata":"https://www.wikidata.org/wiki/Q1232438","display_name":"Umbilical vein","level":3,"score":0.8014000058174133},{"id":"https://openalex.org/C2778326061","wikidata":"https://www.wikidata.org/wiki/Q1761022","display_name":"Enos","level":4,"score":0.7278000116348267},{"id":"https://openalex.org/C2776145790","wikidata":"https://www.wikidata.org/wiki/Q419808","display_name":"Tetrahydrobiopterin","level":4,"score":0.6622999906539917},{"id":"https://openalex.org/C519581460","wikidata":"https://www.wikidata.org/wiki/Q207843","display_name":"Nitric oxide","level":2,"score":0.6531999707221985},{"id":"https://openalex.org/C2780972559","wikidata":"https://www.wikidata.org/wiki/Q550061","display_name":"Endothelial dysfunction","level":2,"score":0.631600022315979},{"id":"https://openalex.org/C2780183776","wikidata":"https://www.wikidata.org/wiki/Q3214147","display_name":"Porphyromonas gingivalis","level":3,"score":0.5130000114440918},{"id":"https://openalex.org/C134018914","wikidata":"https://www.wikidata.org/wiki/Q162606","display_name":"Endocrinology","level":1,"score":0.5083000063896179},{"id":"https://openalex.org/C2778754761","wikidata":"https://www.wikidata.org/wiki/Q421804","display_name":"Lipopolysaccharide","level":2,"score":0.5004000067710876},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.48899999260902405},{"id":"https://openalex.org/C2776992346","wikidata":"https://www.wikidata.org/wiki/Q111140","display_name":"Endothelium","level":2,"score":0.45750001072883606},{"id":"https://openalex.org/C2777834122","wikidata":"https://www.wikidata.org/wiki/Q5939177","display_name":"Human umbilical vein endothelial cell","level":4,"score":0.447299987077713},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.41019999980926514},{"id":"https://openalex.org/C2777622882","wikidata":"https://www.wikidata.org/wiki/Q417619","display_name":"Nitric oxide synthase","level":3,"score":0.40959998965263367},{"id":"https://openalex.org/C123012128","wikidata":"https://www.wikidata.org/wiki/Q5376430","display_name":"Endothelial stem cell","level":3,"score":0.3896999955177307},{"id":"https://openalex.org/C88045685","wikidata":"https://www.wikidata.org/wiki/Q174576","display_name":"Activator (genetics)","level":3,"score":0.3855000138282776},{"id":"https://openalex.org/C2908688039","wikidata":"https://www.wikidata.org/wiki/Q408853","display_name":"Nitric Oxide Synthase Type III","level":5,"score":0.35420000553131104},{"id":"https://openalex.org/C28406088","wikidata":"https://www.wikidata.org/wiki/Q5571762","display_name":"Extracellular","level":2,"score":0.35179999470710754},{"id":"https://openalex.org/C2778827303","wikidata":"https://www.wikidata.org/wiki/Q7558945","display_name":"Soluble guanylyl cyclase","level":4,"score":0.3411000072956085},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.3402999937534332},{"id":"https://openalex.org/C2777451243","wikidata":"https://www.wikidata.org/wiki/Q408256","display_name":"Biopterin","level":5,"score":0.31619998812675476},{"id":"https://openalex.org/C2779679481","wikidata":"https://www.wikidata.org/wiki/Q13581432","display_name":"Plasminogen activator","level":2,"score":0.31200000643730164},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.30720001459121704},{"id":"https://openalex.org/C2776914184","wikidata":"https://www.wikidata.org/wiki/Q101991","display_name":"Inflammation","level":2,"score":0.3052999973297119},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.30300000309944153},{"id":"https://openalex.org/C63645605","wikidata":"https://www.wikidata.org/wiki/Q103191","display_name":"Homeostasis","level":2,"score":0.29120001196861267},{"id":"https://openalex.org/C48349386","wikidata":"https://www.wikidata.org/wiki/Q424361","display_name":"Reactive oxygen species","level":2,"score":0.29100000858306885},{"id":"https://openalex.org/C2776151105","wikidata":"https://www.wikidata.org/wiki/Q898814","display_name":"Oxidative stress","level":2,"score":0.2799000144004822},{"id":"https://openalex.org/C2777952866","wikidata":"https://www.wikidata.org/wiki/Q24722601","display_name":"GLUT1","level":4,"score":0.2752000093460083},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.2676999866962433},{"id":"https://openalex.org/C127561419","wikidata":"https://www.wikidata.org/wiki/Q224527","display_name":"Downregulation and upregulation","level":3,"score":0.25380000472068787}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.20944/preprints202611.1108.v1","doi":"https://doi.org/10.20944/preprints202611.1108.v1","is_oa":true,"landing_page_url":"https://doi.org/10.20944/preprints202611.1108.v1","pdf_url":null,"source":{"id":"https://openalex.org/S6309402219","display_name":"Preprints.org","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":["https://openalex.org/P4310310987"],"host_organization_lineage_names":["Multidisciplinary Digital Publishing Institute"],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.20944/preprints202611.1108.v1","doi":"https://doi.org/10.20944/preprints202611.1108.v1","is_oa":true,"landing_page_url":"https://doi.org/10.20944/preprints202611.1108.v1","pdf_url":null,"source":{"id":"https://openalex.org/S6309402219","display_name":"Preprints.org","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":["https://openalex.org/P4310310987"],"host_organization_lineage_names":["Multidisciplinary Digital Publishing Institute"],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"posted-content"},"sustainable_development_goals":[],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":[],"abstract_inverted_index":{"Periodontitis":[0],"is":[1],"associated":[2],"with":[3,77,88],"vascular":[4,202],"endothelial":[5,22,33,52,184],"dysfunction":[6,185],"and":[7,44,67,98,107,117,134,143,146,149,157,166,186,192],"elevated":[8],"cardiovascular":[9],"risk,":[10],"but":[11],"the":[12,59,68,174],"mechanisms":[13],"by":[14,102],"which":[15],"Porphyromonas":[16],"gingivalis-derived":[17],"lipopolysaccharide":[18],"(Pg.":[19],"LPS)":[20],"impair":[21],"function":[23],"remain":[24],"poorly":[25],"understood.":[26],"We":[27],"investigated":[28],"whether":[29],"Pg.":[30,78,110,182],"LPS":[31,79,111],"disrupts":[32],"homeostasis":[34],"through":[35],"oxidative":[36],"stress,":[37],"tetrahydrobiopterin":[38],"(BH4)":[39],"metabolism,":[40],"nitric":[41],"oxide":[42],"signaling,":[43,114],"glucose":[45,150],"metabolism":[46,191],"in":[47,75],"primary":[48],"human":[49],"umbilical":[50],"vein":[51],"cells":[53],"(HUVECs).":[54],"In":[55],"addition,":[56],"we":[57],"evaluated":[58],"protective":[60],"effects":[61],"of":[62,126,173,181],"L-sepiapterin":[63,91],"(a":[64],"BH4":[65,156,190],"precursor)":[66],"Nrf2":[69,193],"activator":[70],"CDDO-Me.":[71],"HUVECs":[72],"were":[73,100],"treated":[74],"vitro":[76],"(10":[80],"\u03bcg/mL)":[81],"for":[82,200],"12,":[83],"24,":[84],"or":[85,89,94],"48":[86],"h,":[87],"without":[90],"(100":[92,96],"\u03bcM)":[93],"CDDO-Me":[95,161],"nM),":[97],"outcomes":[99],"assessed":[101],"qRT-PCR,":[103],"Western":[104],"blot,":[105],"ELISA,":[106],"biochemical":[108],"assays.":[109],"activated":[112],"TLR4/NF-\u03baB":[113],"increased":[115,137,144],"ROS":[116],"ICAM-1,":[118],"suppressed":[119,164],"Nrf2.":[120],"It":[121],"produced":[122],"a":[123,178],"biphasic":[124],"disruption":[125,172],"GCH1/DHFR":[127],"expression;":[128,139],"reduced":[129],"extracellular":[130],"BH4,":[131],"eNOS":[132,135,158],"expression,":[133],"dimerization;":[136],"iNOS":[138,165],"altered":[140],"nitrite":[141],"output;":[142],"PEA-15":[145],"GLUT1":[147],"expression":[148],"uptake.":[151],"L-Sepiapterin":[152],"more":[153,162],"consistently":[154],"restored":[155],"coupling,":[159],"whereas":[160],"effectively":[163],"oxidative/inflammatory":[167],"markers.":[168],"These":[169],"findings":[170],"identify":[171],"GCH1/DHFR\u2013BH4\u2013eNOS":[175],"axis":[176],"as":[177],"key":[179],"mechanism":[180],"LPS-induced":[183],"suggest":[187],"that":[188],"targeting":[189],"signaling":[194],"may":[195],"be":[196],"complementary":[197],"therapeutic":[198],"strategies":[199],"periodontitis-associated":[201],"disease.":[203]},"counts_by_year":[],"updated_date":"2026-11-12T12:28:57.059296","created_date":"2026-11-12T00:00:00"}