{"doi":"10.1101/2024.04.22.590484","title":"Short-Term Disruption of TGFβ Signaling in Adult Mice Renders the Aorta Vulnerable to Hypertension-Induced Dissection","abstract":"Hypertension and transient increases in blood pressure from extreme exertion are risk factors for aortic dissection in patients with age-related vascular degeneration or inherited connective tissue disorders. Yet, the common experimental model of angiotensin II-induced aortopathy in mice appears independent of high blood pressure as lesions do not occur in response to an alternative vasoconstrictor, norepinephrine, and are not prevented by co-treatment with a vasodilator, hydralazine. We investigated vasoconstrictor administration to adult mice 1 week after disruption of TGFβ signaling in smooth muscle cells. Norepinephrine increased blood pressure and induced aortic dissection by 7 days and even within 30 minutes that was rescued by hydralazine; results were similar with angiotensin II. Changes in regulatory contractile molecule expression were not of pathological significance. Rather, reduced synthesis of extracellular matrix yielded a vulnerable aortic phenotype by decreasing medial collagen, most dynamically type XVIII, and impairing cell-matrix adhesion. We conclude that transient and sustained increases in blood pressure cause dissection in aortas rendered vulnerable by inhibition of TGFβ-driven extracellular matrix production by smooth muscle cells. A corollary is that medial fibrosis, a frequent feature of medial degeneration, may afford some protection against aortic dissection.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":490809,"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":0.9466,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":668390,"name":"Pengwei Ren","orcid":"0000-0003-2853-412X","position":1,"is_corresponding":false},{"id":280162,"name":"Changshun He","orcid":null,"position":2,"is_corresponding":false},{"id":891918,"name":"Mo Wang","orcid":"0000-0001-7004-3549","position":3,"is_corresponding":false},{"id":245123,"name":"Sae‐Il Murtada","orcid":"0000-0002-6578-4585","position":4,"is_corresponding":false},{"id":1336002,"name":"Yu Chen","orcid":"0009-0008-5331-0463","position":5,"is_corresponding":false},{"id":268874,"name":"Abhay B. Ramachandra","orcid":"0000-0001-6275-501X","position":6,"is_corresponding":false},{"id":675705,"name":"Guangxin Li","orcid":"0000-0002-4546-0268","position":7,"is_corresponding":false},{"id":245120,"name":"Lingfeng Qin","orcid":"0000-0002-5381-6826","position":8,"is_corresponding":false},{"id":536474,"name":"Roland Assi","orcid":"0000-0002-0863-9867","position":9,"is_corresponding":false},{"id":270346,"name":"Martin A. Schwartz","orcid":"0000-0002-2071-1243","position":10,"is_corresponding":false},{"id":245130,"name":"Jay D. Humphrey","orcid":"0000-0003-1011-2025","position":11,"is_corresponding":false},{"id":245131,"name":"George Tellides","orcid":"0000-0001-7042-8190","position":12,"is_corresponding":false},{"id":245126,"name":"Bo Jiang","orcid":"0000-0003-1261-7705","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:08:37.162700Z","pmid":"38712205","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":[]}