{"doi":"10.1016/j.bvth.2025.100110","title":"Mitochondrial arginase 2 regulates hematopoietic and cardiovascular adaptation to hypoxia","abstract":"Physiological adaptation to hypoxia involves coordinated responses of the hematopoietic and cardiovascular systems to maintain tissue oxygenation. Arginine metabolism, via nitric oxide synthases and arginases, modulates both erythropoiesis and vascular tone. Arginase 2 ( Arg2 ), a mitochondrial enzyme, may regulate these responses by limiting arginine availability for nitric oxide (NO) production. We hypothesized that deletion of Arg2 ( Arg2 knockout [ Arg2 KO]) would augment NO bioavailability, attenuate hypoxia-driven hematopoiesis, and protect against pulmonary vascular remodeling. To test this, we exposed Arg2 KO and wild-type (WT) mice to normoxia, short-term (6-72 hours) or chronic (3 weeks) hypoxia. In comparison with WT, Arg2 KO mice under normoxia had fewer erythroid progenitors, comparable hematologic and cardiovascular parameters, but greater numbers of small vessels in the lungs. Under short-term hypoxia, Arg2 KO mice had a blunted erythropoietic response, with elevated plasma arginine and NO metabolites as compared with WT mice. Under chronic hypoxia, WT mice developed elevated right ventricular systolic pressure (RVSP) and remodeling of small pulmonary vessels. In contrast, Arg2 KO mice did not increase RVSP or small vessel remodeling and maintained lower systemic blood pressure and heart rate compared with WT mice. Metabolically, endothelial cells from Arg2 KO mice lungs demonstrated upregulation of arginine biosynthetic and fatty acid β-oxidation pathways, accompanied by less myocardial lipid droplet accumulation. These findings identify a previously unrecognized role for mitochondrial ARG2 in regulating hematopoietic and vascular adaptation to hypoxia through modulation of nitric oxide signaling and metabolic reprogramming.","journal":"Blood Vessels Thrombosis & Hemostasis","year":2025,"id":547530,"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":0.9586,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":280250,"name":"Kewal Asosingh","orcid":null,"position":1,"is_corresponding":false},{"id":280248,"name":"Allison J. Janocha","orcid":null,"position":2,"is_corresponding":false},{"id":1074061,"name":"Evan Madden","orcid":null,"position":3,"is_corresponding":false},{"id":294463,"name":"Nicholas Wanner","orcid":"0000-0003-1156-1527","position":4,"is_corresponding":false},{"id":1317050,"name":"Dylan Trotter","orcid":null,"position":5,"is_corresponding":false},{"id":484102,"name":"Michael Novotny","orcid":null,"position":6,"is_corresponding":false},{"id":289086,"name":"Anny Mulya","orcid":"0000-0002-6008-1514","position":7,"is_corresponding":false},{"id":1440383,"name":"Ruoying Chen","orcid":null,"position":8,"is_corresponding":false},{"id":249757,"name":"Samar Farha","orcid":"0000-0003-4800-8928","position":9,"is_corresponding":false},{"id":228050,"name":"Serpil C. Erzurum","orcid":"0000-0001-5202-9065","position":10,"is_corresponding":false},{"id":304127,"name":"Weiling Xu","orcid":"0000-0003-1572-4311","position":0,"is_corresponding":true}],"reference_count":77,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:53:41.314800Z","pmid":"41458148","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":[]}