{"doi":"10.1007/s00395-021-00862-y","title":"Fibroblast GATA-4 and GATA-6 promote myocardial adaptation to pressure overload by enhancing cardiac angiogenesis","abstract":"Heart failure due to high blood pressure or ischemic injury remains a major problem for millions of patients worldwide. Despite enormous advances in deciphering the molecular mechanisms underlying heart failure progression, the cell-type specific adaptations and especially intercellular signaling remain poorly understood. Cardiac fibroblasts express high levels of cardiogenic transcription factors such as GATA-4 and GATA-6, but their role in fibroblasts during stress is not known. Here, we show that fibroblast GATA-4 and GATA-6 promote adaptive remodeling in pressure overload induced cardiac hypertrophy. Using a mouse model with specific single or double deletion of Gata4 and Gata6 in stress activated fibroblasts, we found a reduced myocardial capillarization in mice with Gata4/6 double deletion following pressure overload, while single deletion of Gata4 or Gata6 had no effect. Importantly, we confirmed the reduced angiogenic response using an in vitro co-culture system with Gata4/6 deleted cardiac fibroblasts and endothelial cells. A comprehensive RNA-sequencing analysis revealed an upregulation of anti-angiogenic genes upon Gata4/6 deletion in fibroblasts, and siRNA mediated downregulation of these genes restored endothelial cell growth. In conclusion, we identified a novel role for the cardiogenic transcription factors GATA-4 and GATA-6 in heart fibroblasts, where both proteins act in concert to promote myocardial capillarization and heart function by directing intercellular crosstalk.","journal":"Basic Research in Cardiology","year":2021,"id":156465,"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":54,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9529,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":662480,"name":"Natali Froese","orcid":null,"position":1,"is_corresponding":false},{"id":661403,"name":"Xue Wang","orcid":"0009-0004-2529-8656","position":2,"is_corresponding":false},{"id":662481,"name":"Hannah Kroeger","orcid":null,"position":3,"is_corresponding":false},{"id":399796,"name":"Honghui Wang","orcid":"0000-0002-9318-3023","position":4,"is_corresponding":false},{"id":661404,"name":"Malgorzata Szaroszyk","orcid":"0009-0008-4051-3958","position":5,"is_corresponding":false},{"id":661405,"name":"Mona Malek Mohammadi","orcid":"0000-0001-8410-7865","position":6,"is_corresponding":false},{"id":661406,"name":"Julio Cordero","orcid":"0000-0002-2136-1783","position":7,"is_corresponding":false},{"id":661407,"name":"Merve Keleş","orcid":"0000-0002-5212-3753","position":8,"is_corresponding":false},{"id":661408,"name":"Mortimer Korf‐Klingebiel","orcid":"0000-0002-4388-2117","position":9,"is_corresponding":false},{"id":661409,"name":"Kai C. Wollert","orcid":"0000-0002-4890-4450","position":10,"is_corresponding":false},{"id":57957,"name":"Robert Geffers","orcid":"0000-0003-4409-016X","position":11,"is_corresponding":false},{"id":282922,"name":"Manuel Mayr","orcid":"0000-0002-0597-829X","position":12,"is_corresponding":false},{"id":360617,"name":"Simon J. Conway","orcid":"0000-0001-5593-9259","position":13,"is_corresponding":false},{"id":661410,"name":"Gergana Dobreva","orcid":"0000-0002-4814-9416","position":14,"is_corresponding":false},{"id":661411,"name":"Johann Bauersachs","orcid":"0000-0002-9341-117X","position":15,"is_corresponding":false},{"id":597449,"name":"Joerg Heineke","orcid":"0000-0002-1541-3030","position":16,"is_corresponding":false},{"id":661402,"name":"Gesine M. Dittrich","orcid":"0000-0002-9053-078X","position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-18T23:44:13.017332Z","pmid":"33876316","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":[]}