{"doi":"10.3389/fcvm.2022.871852","title":"Hydrogen Peroxide Scavenging Restores N-Type Calcium Channels in Cardiac Vagal Postganglionic Neurons and Mitigates Myocardial Infarction-Evoked Ventricular Arrhythmias in Type 2 Diabetes Mellitus","abstract":"Objective Withdrawal of cardiac vagal activity is associated with ventricular arrhythmia-related high mortality in patients with type 2 diabetes mellitus (T2DM). Our recent study found that reduced cell excitability of cardiac vagal postganglionic (CVP) neurons is involved in cardiac vagal dysfunction and further exacerbates myocardial infarction (MI)-evoked ventricular arrhythmias and mortality in T2DM. However, the mechanisms responsible for T2DM-impaired cell excitability of CVP neurons remain unclear. This study tested if and how elevation of hydrogen peroxide (H 2 O 2 ) inactivates CVP neurons and contributes to cardiac vagal dysfunction and ventricular arrhythmogenesis in T2DM. Methods and Results Rat T2DM was induced by a high-fat diet plus streptozotocin injection. Local in vivo transfection of adenoviral catalase gene (Ad.CAT) successfully induced overexpression of catalase and subsequently reduced cytosolic H 2 O 2 levels in CVP neurons in T2DM rats. Ad.CAT restored protein expression and ion currents of N-type Ca 2+ channels and increased cell excitability of CVP neurons in T2DM. Ad.CAT normalized T2DM-impaired cardiac vagal activation, vagal control of ventricular function, and heterogeneity of ventricular electrical activity. Additionally, Ad.CAT not only reduced the susceptibility to ventricular arrhythmias, but also suppressed MI-evoked lethal ventricular arrhythmias such as VT/VF in T2DM. Conclusions We concluded that endogenous H 2 O 2 elevation inhibited protein expression and activation of N-type Ca 2+ channels and reduced cell excitability of CVP neurons, which further contributed to the withdrawal of cardiac vagal activity and ventricular arrhythmogenesis in T2DM. Our current study suggests that the H 2 O 2 -N-type Ca 2+ channel signaling axis might be an effective therapeutic target to suppress ventricular arrhythmias in T2DM patients with MI.","journal":"Frontiers in Cardiovascular Medicine","year":2022,"id":277659,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9532,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":826951,"name":"Huiyin Tu","orcid":null,"position":1,"is_corresponding":false},{"id":290936,"name":"Wenfeng Hu","orcid":"0000-0002-2571-3889","position":2,"is_corresponding":false},{"id":367137,"name":"Bin Duan","orcid":"0000-0003-3302-1900","position":3,"is_corresponding":false},{"id":284842,"name":"Matthew C. Zimmerman","orcid":"0000-0001-5658-9051","position":4,"is_corresponding":false},{"id":827037,"name":"Yu‐Long Li","orcid":"0000-0001-5407-2761","position":5,"is_corresponding":false},{"id":826652,"name":"Dongze Zhang","orcid":"0000-0002-5510-5972","position":0,"is_corresponding":true}],"reference_count":115,"raw_metadata":null,"created_at":"2026-07-19T00:28:39.226969Z","pmid":"35548411","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":[]}