{"doi":"10.3390/ijms241310994","title":"Exposure to Stress Alters Cardiac Gene Expression and Exacerbates Myocardial Ischemic Injury in the Female Murine Heart","abstract":"Mental stress is a risk factor for myocardial infarction in women. The central hypothesis of this study is that restraint stress induces sex-specific changes in gene expression in the heart, which leads to an intensified response to ischemia/reperfusion injury due to the development of a pro-oxidative environment in female hearts. We challenged male and female C57BL/6 mice in a restraint stress model to mimic the effects of mental stress. Exposure to restraint stress led to sex differences in the expression of genes involved in cardiac hypertrophy, inflammation, and iron-dependent cell death (ferroptosis). Among those genes, we identified tumor protein p53 and cyclin-dependent kinase inhibitor 1A (p21), which have established controversial roles in ferroptosis. The exacerbated response to I/R injury in restraint-stressed females correlated with downregulation of p53 and nuclear factor erythroid 2-related factor 2 (Nrf2, a master regulator of the antioxidant response system-ARE). S-female hearts also showed increased superoxide levels, lipid peroxidation, and prostaglandin-endoperoxide synthase 2 (Ptgs2) expression (a hallmark of ferroptosis) compared with those of their male counterparts. Our study is the first to test the sex-specific impact of restraint stress on the heart in the setting of I/R and its outcome.","journal":"International Journal of Molecular Sciences","year":2023,"id":349748,"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":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9542,"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":765699,"name":"Lilly Kamberov","orcid":"0000-0002-7724-5124","position":1,"is_corresponding":false},{"id":766294,"name":"Natalie Carroll","orcid":null,"position":2,"is_corresponding":false},{"id":765698,"name":"Shripa Amatya","orcid":"0009-0003-8190-7164","position":3,"is_corresponding":false},{"id":1093270,"name":"D. Djukic Cosic","orcid":"0000-0002-7788-6423","position":4,"is_corresponding":false},{"id":921911,"name":"Oscar Gómez","orcid":"0000-0001-5492-3343","position":5,"is_corresponding":false},{"id":639869,"name":"Shantel Vital","orcid":null,"position":6,"is_corresponding":false},{"id":260321,"name":"Farzane Sivandzade","orcid":"0000-0001-8649-3712","position":7,"is_corresponding":false},{"id":260320,"name":"Aditya Bhalerao","orcid":"0009-0006-4966-0714","position":8,"is_corresponding":false},{"id":1025839,"name":"Salvatore Mancuso","orcid":"0000-0002-9874-2234","position":9,"is_corresponding":false},{"id":327074,"name":"Xinggui Shen","orcid":"0000-0002-4002-9671","position":10,"is_corresponding":false},{"id":372532,"name":"Hyung Wook Nam","orcid":"0000-0002-8294-7403","position":11,"is_corresponding":false},{"id":344652,"name":"A. Wayne Orr","orcid":"0000-0002-2377-213X","position":12,"is_corresponding":false},{"id":469690,"name":"Tanja Dudenbostel","orcid":"0000-0003-3260-8363","position":13,"is_corresponding":false},{"id":626039,"name":"Steven R. Bailey","orcid":"0000-0002-5792-6926","position":14,"is_corresponding":false},{"id":226777,"name":"Christopher G. Kevil","orcid":"0000-0003-0863-7260","position":15,"is_corresponding":false},{"id":105404,"name":"Luca Cucullo","orcid":"0000-0002-2827-7162","position":16,"is_corresponding":false},{"id":443573,"name":"Diana Cruz‐Topete","orcid":"0000-0001-6315-6027","position":17,"is_corresponding":false},{"id":315557,"name":"Hemangini A. Dhaibar","orcid":"0000-0002-4120-4910","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-19T01:12:19.059218Z","pmid":"37446174","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":[]}