{"doi":"10.17615/rxd4-b561","title":"The smooth muscle-selective RhoGAP GRAF3 is a critical regulator of vascular tone and hypertension","abstract":"Although hypertension is a worldwide health issue, an incomplete understanding of its etiology has hindered our ability to treat this complex disease. Here we identify arhgap42 (also known as GRAF3) as a Rho-specific GAP expressed specifically in smooth muscle cells in mice and humans. We show that GRAF3-deficient mice exhibit significant hypertension and increased pressor responses to angiotensin II and endothelin-1; these effects are prevented by treatment with the Rho-kinase inhibitor, Y-27632. RhoA activity and myosin light chain phosphorylation are elevated in GRAF3-depleted smooth muscle cells in vitro and in vivo, and isolated vessel segments from GRAF3-deficient mice show increased contractility. Taken together our data indicate that GRAF3-mediated inhibition of RhoA activity in vascular smooth muscle cells is necessary for maintaining normal blood pressure homeostasis. Moreover, these findings provide a potential mechanism for a hypertensive locus recently identified within arhgap42 and provide a foundation for the future development of innovative hypertension therapies.","journal":"UNC Libraries","year":2020,"id":117376,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9568,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":544990,"name":"Kim E. Bird","orcid":null,"position":1,"is_corresponding":false},{"id":436448,"name":"Masao Kakoki","orcid":"0000-0001-5177-1014","position":2,"is_corresponding":false},{"id":237173,"name":"Mauricio Rojas","orcid":"0000-0001-7340-4784","position":3,"is_corresponding":false},{"id":365966,"name":"Alisa A. Suen","orcid":"0000-0002-0639-9177","position":4,"is_corresponding":false},{"id":547750,"name":"Kaitlin C. Lenhart","orcid":null,"position":5,"is_corresponding":false},{"id":245728,"name":"Feng Li","orcid":"0000-0002-9680-4614","position":6,"is_corresponding":false},{"id":546958,"name":"Xue Bai","orcid":"0000-0001-9717-846X","position":7,"is_corresponding":false},{"id":442230,"name":"Christopher P. Mack","orcid":"0000-0001-6713-0844","position":8,"is_corresponding":false},{"id":307175,"name":"Joan M. Taylor","orcid":"0000-0002-8794-5167","position":9,"is_corresponding":false},{"id":45210,"name":"Oliver Smithies","orcid":"0000-0002-4934-3931","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:13:51.309289Z","pmid":null,"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":[]}