{"doi":"10.1016/j.isci.2020.101863","title":"Differential Regulation of mTOR Complexes with miR-302a Attenuates Myocardial Reperfusion Injury in Diabetes","abstract":"Persistent activation of mTOR (mammalian target of rapamycin) in diabetes increases the vulnerability of the heart to ischemia/reperfusion (I/R) injury. We show here that infusion of rapamycin (mTOR inhibitor) at reperfusion following ischemia reduced myocardial infarct size and apoptosis with restoration of cardiac function in type 1 diabetic rabbits. Likewise, treatment with rapamycin protected hyperglycemic human-pluripotent-stem-cells-derived cardiomyocytes (HG-hiPSC-CMs) following simulated ischemia (SI) and reoxygenation (RO). Phosphorylation of S6 (mTORC1 marker) was increased, whereas AKT phosphorylation (mTORC2 marker) and microRNA-302a were reduced with concomitant increase of its target, PTEN, following I/R injury in diabetic heart and HG-hiPSC-CMs. Rapamycin inhibited mTORC1 and PTEN, but augmented mTORC2 with restoration of miRNA-302a under diabetic conditions. Inhibition of miRNA-302a blocked mTORC2 and abolished rapamycin-induced protection against SI/RO injury in HG-hiPSC-CMs. We conclude that rapamycin attenuates reperfusion injury in diabetic heart through inhibition of PTEN and mTORC1 with restoration of miR-302a-mTORC2 signaling.","journal":"iScience","year":2020,"id":79077,"datarank":0.4335557636844247,"base_score":2.8903717578961645,"endowment":2.8903717578961645,"self_citation_contribution":0.4335557636844247,"citation_network_contribution":0.0,"self_endowment_contribution":0.4335557636844247,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":17,"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":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":412531,"name":"Ramzi Ockaili","orcid":null,"position":1,"is_corresponding":false},{"id":401105,"name":"Chad Cain","orcid":null,"position":2,"is_corresponding":false},{"id":412532,"name":"Sean K. Roh","orcid":null,"position":3,"is_corresponding":false},{"id":412533,"name":"Scott M. Filippone","orcid":null,"position":4,"is_corresponding":false},{"id":412534,"name":"Donatas Kraskauskas","orcid":null,"position":5,"is_corresponding":false},{"id":365976,"name":"Rakesh C. Kukreja","orcid":"0000-0001-9484-3743","position":6,"is_corresponding":false},{"id":299128,"name":"Anindita Das","orcid":"0000-0003-4422-7277","position":7,"is_corresponding":false},{"id":299127,"name":"Arun Samidurai","orcid":"0000-0002-5360-2553","position":0,"is_corresponding":true}],"reference_count":81,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T21:50:33.748601Z","pmid":"33319180","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":[]}