{"doi":"10.1126/sciadv.abg1694","title":"Single-cell RNA-seq reveals a critical role of novel pro-inflammatory EndMT in mediating adverse remodeling in coronary artery–on–a–chip","abstract":"A three-dimensional microengineered human coronary artery-on-a-chip was developed for investigation of the mechanism by which low and oscillatory shear stress (OSS) induces pro-atherogenic changes. Single-cell RNA sequencing revealed that OSS induced distinct changes in endothelial cells (ECs) including pro-inflammatory endothelial-to-mesenchymal transition (EndMT). OSS promoted pro-inflammatory EndMT through the Notch1/p38 MAPK-NF-κB signaling axis. Moreover, OSS-induced EC phenotypic changes resulted in proliferation and extracellular matrix (ECM) protein up-regulation in smooth muscle cells (SMCs) through the RANTES-mediated paracrine mechanism. IL-37 suppressed OSS-induced pro-inflammatory EndMT and thereby abrogated SMC proliferation and ECM protein remodeling. Overall, this study provides insights into endothelial heterogeneity under atheroprone shear stress and identifies the mechanistic role of a novel EC subtype in promoting adverse vascular remodeling. Further, this study demonstrates that anti-inflammatory approach is capable of mitigating vascular pathobiology evoked by atheroprone shear stress.","journal":"Science Advances","year":2021,"id":158184,"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":47,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9595,"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":416807,"name":"Qingzhou Yao","orcid":null,"position":1,"is_corresponding":false},{"id":415471,"name":"Peijian Zhang","orcid":"0009-0003-1468-1417","position":2,"is_corresponding":false},{"id":415470,"name":"Erlinda The","orcid":"0000-0003-2475-4715","position":3,"is_corresponding":false},{"id":416808,"name":"Yufeng Zhai","orcid":null,"position":4,"is_corresponding":false},{"id":416809,"name":"Lihua Ao","orcid":null,"position":5,"is_corresponding":false},{"id":388856,"name":"Michael J. Jarrett","orcid":"0000-0003-2959-8555","position":6,"is_corresponding":false},{"id":235545,"name":"Charles A. Dinarello","orcid":"0000-0002-5073-8316","position":7,"is_corresponding":false},{"id":107537,"name":"David A. Fullerton","orcid":"0000-0002-6895-6354","position":8,"is_corresponding":false},{"id":388858,"name":"Xianzhong Meng","orcid":"0000-0002-0201-1008","position":9,"is_corresponding":false},{"id":666576,"name":"Peng Zhao","orcid":"0000-0003-3499-1415","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-07-18T23:44:26.210708Z","pmid":"34417174","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":[]}