{"doi":"10.1101/2023.08.10.552881","title":"Ovariectomy-Induced Arterial Stiffening Differs from Vascular Aging and is Reversed by GPER Activation","abstract":"Arterial stiffness is a cardiovascular risk factor and dramatically increases as women transition through menopause. The current study assessed whether a mouse model of menopause increases arterial stiffness in a similar manner to aging, and whether activation of the G protein-coupled estrogen receptor (GPER) could reverse stiffness. Female C57Bl/6J mice were ovariectomized (OVX) at 10 weeks of age or aged to 52 weeks, and some mice were treated with GPER agonists. OVX and aging increased pulse wave velocity to a similar extent independent of changes in blood pressure. Aging increased carotid wall thickness, while OVX increased material stiffness without altering vascular geometry. RNA-Seq analysis revealed that OVX downregulated smooth muscle contractile genes. The enantiomerically pure GPER agonist, LNS8801, reversed stiffness in OVX mice to a greater degree than the racemic agonist G-1. In summary, OVX and aging induced arterial stiffening via potentially different mechanisms. Aging was associated with inward remodeling while OVX induced material stiffness independent of geometry and a loss of the contractile phenotype. This study helps to further our understanding of the impact of menopause on vascular health and identifies LNS8801 as a potential therapy to counteract this detrimental process in women.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":391456,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9612,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1002505,"name":"Alexandra B. McNally","orcid":"0000-0001-5516-4991","position":1,"is_corresponding":false},{"id":688888,"name":"Tristen J. Wong","orcid":null,"position":2,"is_corresponding":false},{"id":388203,"name":"Bruna Visniauskas","orcid":"0000-0002-4525-2194","position":3,"is_corresponding":false},{"id":424068,"name":"Sophia Blessinger","orcid":"0000-0001-5742-4144","position":4,"is_corresponding":false},{"id":1164178,"name":"Ariane Imulinde Sugi","orcid":"0009-0003-8519-5184","position":5,"is_corresponding":false},{"id":1164662,"name":"Chase Richard","orcid":null,"position":6,"is_corresponding":false},{"id":1164663,"name":"Zaidmara Díaz","orcid":null,"position":7,"is_corresponding":false},{"id":981205,"name":"Alec C. Horton","orcid":null,"position":8,"is_corresponding":false},{"id":296415,"name":"Christopher A. Natale","orcid":"0000-0003-4949-3849","position":9,"is_corresponding":false},{"id":688428,"name":"Benard O. Ogola","orcid":"0000-0002-6084-6986","position":10,"is_corresponding":false},{"id":411982,"name":"Sarah H. Lindsey","orcid":"0000-0002-9837-4582","position":11,"is_corresponding":false},{"id":688430,"name":"Isabella Kilanowski‐Doroh","orcid":"0000-0003-4998-8171","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-19T01:18:47.408273Z","pmid":"37645992","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}