{"doi":"10.1164/rccm.202302-0284ed","title":"SOX17 at the Intersection of Sex, Transcription, and Metabolism in Pulmonary Hypertension","abstract":"Pulmonary arterial hypertension (PAH) is an incurable and devastating disease characterized by pulmonary vascular remodeling, increased pulmonary vascular resistance, and right heart failure.Genetic mutations account for 23.5% of PAH cases (1).Among known mutations, there is considerable genetic heterogeneity from a diverse collection of rare heterozygous coding-region mutations.One such genetic mutation affects SOX17 (SRY-related HMG-box17) (1).SOX17 is a key endothelial-specific transcription factor involved in angiogenesis (2), induction of tip cell differentiation (3), arteriovenous differentiation (4), and pulmonary endothelial regeneration following vascular injury (5).PAH secondary to deleterious SOX17 variants is associated with congenital heart disease (6) and clinically presents with severe hemodynamic derangements (mean pulmonary arterial pressure of 67 mm Hg and pulmonary vascular resistance of 14.0 Wood units) (7).Recently, a common genetic variant in the enhancer region of SOX17 was found through a genome-wide association study in an international cohort of patients with PAH (8).This discovery raised the question of the contribution of SOX17 as a risk allele for PAH.In this issue of the Journal, Sangam and colleagues (pp.1055-1069) proposed that SOX17 deficiency promotes PAH through interactions with hypoxia-inducible factor 2a (HIF2a) and estrogen pathways, as well as dysfunctional mitochondrial metabolism (9).The authors first noted decreased endothelial-specific SOX17 expression in human pulmonary artery endothelial cells isolated from patients with PAH and in rats with chronic hypoxiainduced pulmonary hypertension (PH) and monocrotaline PH.Using an inducible conditional Tie2-Sox17 knockout murine model, the authors found that exposure of Sox17-deficient mice to hypoxia resulted in pulmonary vascular remodeling, increased right-sided pressure, and right ventricular hypertrophy.Conversely, Sox17-transgenic overexpression in mice attenuated hypoxic PH","journal":"American Journal of Respiratory and Critical Care Medicine","year":2023,"id":376652,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9563,"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":260643,"name":"David B. Frank","orcid":"0000-0002-3064-2069","position":1,"is_corresponding":false},{"id":323519,"name":"Susan M. Lin","orcid":"0000-0002-2415-8350","position":0,"is_corresponding":true}],"reference_count":13,"raw_metadata":null,"created_at":"2026-07-19T01:16:32.368674Z","pmid":"36927296","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":[]}