{"doi":"10.3389/fphys.2025.1565917","title":"S-nitrosylation of cardiac myocyte proteins may underlie sex differences in cardiac disease","abstract":"Nitric oxide (NO) plays several critical roles in cardiovascular physiology. This molecule regulates cardiac function by modifying Ca 2+ -handling proteins through a process known as S- nitrosylation. These targets include L-type Calcium Channels (LTCC), Ryanodine Receptors (RyR2), Protein Kinase G (PKG), Phospholamban (PLB), sarco/endoplasmic reticulum Ca 2+ -ATPase (SERCA2a) and Ca 2+ /Calmodulin-dependent protein kinase II (CaMKII). S- nitrosylation is a covalent attachment of an NO moiety to the thiol side chain of a cysteine residue within a protein. This process can modify excitation-contraction coupling in cardiomyocytes and may mediate some forms of cardioprotection. Several studies have shown that S -nitrosylation may also be involved in the progression of cardiovascular diseases. Most importantly, recent studies have focused on the molecular mechanisms underlying cardiovascular diseases (CVD). Emerging evidence suggests that sex-specific differences in cardiac protein S- nitrosylation exist, and may partially explain disparities in cardiovascular health in males and females. Females have been found to have higher cardiac protein S- nitrosylation levels compared to men, and this is attributed to enhanced NO production through estrogen. Emerging data suggests that S-nitrosylation of specific proteins such as CaMKII has a dual role of promoting and preventing arrhythmias, it is not clear whether the cardioprotective effect of S -nitrosylation of specific cardiac proteins is sex-dependent. A deeper understanding of the mechanisms regulating the role of protein S-nitrosylation and the impact of sex differences on S-nitrosylation will open new avenues for therapeutic interventions in cardiac diseases.","journal":"Frontiers in Physiology","year":2025,"id":521132,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9521,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1063828,"name":"Raquel E. Parackal","orcid":"0009-0007-5419-4700","position":1,"is_corresponding":false},{"id":649584,"name":"Jeffrey R. Erickson","orcid":"0000-0001-5918-1991","position":2,"is_corresponding":false},{"id":229037,"name":"Donald M. Bers","orcid":"0000-0002-2237-9483","position":3,"is_corresponding":false},{"id":1063826,"name":"Esther Udo Asamudo","orcid":"0000-0003-4800-4417","position":0,"is_corresponding":true}],"reference_count":135,"raw_metadata":null,"created_at":"2026-07-19T02:49:32.958846Z","pmid":"40395646","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":[]}