{"doi":"10.1006/jmcc.2001.1394","title":"Gender Influences on Sarcoplasmic Reticulum Ca2+-handling in Failing Human Myocardium","abstract":null,"journal":"Journal of Molecular and Cellular Cardiology","year":2001,"id":670617,"datarank":0.772993739174667,"base_score":5.153291594497779,"endowment":5.153291594497779,"self_citation_contribution":0.772993739174667,"citation_network_contribution":0.0,"self_endowment_contribution":0.772993739174667,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":172,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":2,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1751741,"name":"Konrad F. Frank","orcid":null,"position":1,"is_corresponding":false},{"id":1751742,"name":"Andrew N. Carr","orcid":null,"position":2,"is_corresponding":false},{"id":30815,"name":"Christine S. Moravec","orcid":"0000-0001-7369-1218","position":3,"is_corresponding":false},{"id":408804,"name":"Evangelia G. Kranias","orcid":"0000-0002-4621-6179","position":4,"is_corresponding":false},{"id":964342,"name":"Rajesh Dash","orcid":"0000-0002-2499-6389","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Gender Influences on Sarcoplasmic Reticulum Ca2+-handling in Failing Human Myocardium","abstract":"Gender has recently been implicated as an important modulator of cardiovascular disease. However, it is not known how gender may specifically influence the Ca2+-handling deficits that characterize the depressed cardiac contractility of human heart failure. To elucidate the contributory role of gender to sarcoplasmic reticulum (SR) Ca2+ cycling alterations, the protein levels of SR Ca2+-ATPase (SERCA), phospholamban, and calsequestrin, as well as the site-specific phospholamban phosphorylation status, were quantified in a mixed gender population of failing (n=14) and donor (n=15) myocardia. The apparent affinity (EC50) and the maximal velocity (Vmax) of SR Ca2+-uptake were also determined to lend functional significance to any observed protein alterations. Phospholamban and calsequestrin levels were not altered; however, SERCA protein levels were significantly reduced in failing hearts. Additionally, phospholamban phosphorylation (serine-16 and threonine-17 sites) and myocardial cAMP content were both attenuated. The alterations in SR protein levels were also accompanied by a decreased V(max)and an increased EC50 (diminished apparent affinity) of SR Ca2+-uptake for Ca2+ in failing myocardia. Myocardial protein levels and Ca2+ uptake parameters were then analyzed with respect to gender, which revealed that the decreases in phosphorylated serine-16 were specific to male failing hearts, reflecting increases in the EC50 values of SR Ca2+-uptake for Ca2+, compared to donor males. These findings suggest that although decreased SERCA protein and phospholamban phosphorylation levels contribute to depressed SR Ca2+-uptake and left ventricular function in heart failure, the specific subcellular alterations which underlie these effects may not be uniform with respect to gender.","is_dataset_classified":null,"base_score":5.153291594497779,"endowment":5.153291594497779,"datacite_reuse_total":2,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"11437540","pmcid":null,"openalex_id":"https://openalex.org/W2015769784","authors":[],"funders":[{"funder_name":"NHLBI NIH HHS","grant_id":"HL26057","title":null},{"funder_name":"NCRR NIH HHS","grant_id":"P40RR12358","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"HL52318","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"HL07382","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"HL64018","title":null}],"total_grants":5,"fwci":6.4753,"citation_percentile":0.97208481,"influential_citations":0,"citation_trend":[{"year":2012,"count":9},{"year":2013,"count":8},{"year":2014,"count":8},{"year":2015,"count":5},{"year":2016,"count":7},{"year":2017,"count":3},{"year":2018,"count":3},{"year":2019,"count":4},{"year":2020,"count":10},{"year":2021,"count":3},{"year":2023,"count":3},{"year":2025,"count":1},{"year":2026,"count":1}],"oa_status":"closed","license":"https://www.elsevier.com/tdm/userlicense/1.0/","oa_locations":[{"url":"https://api.elsevier.com/content/article/PII:S002228280191394X?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S002228280191394X?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1006/jmcc.2001.1394","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/11437540","host_type":"repository"}],"fields_of_study":["Cardiac electrophysiology and arrhythmias","Ion channel regulation and function","Cardiomyopathy and Myosin Studies","Adult","Calcium","Calcium-Binding Proteins","Calcium-Transporting ATPases","Calsequestrin","Cyclic AMP","Female","Heart Failure","Humans","In Vitro Techniques","Male","Middle Aged","Myocardial Contraction","Sarcoplasmic Reticulum","Sex Factors","Phospholamban"],"mesh_terms":["Phospholamban","Cyclic AMP","Calcium-Transporting ATPases","Adult","Calcium","Calcium-Binding Proteins","Calsequestrin","Female","Heart Failure","Humans","Male","Middle Aged","Myocardial Contraction","Sarcoplasmic Reticulum","Sex Factors","In Vitro Techniques"],"keywords":["Phospholamban","Calsequestrin","SERCA","Internal medicine","Contractility","Endoplasmic reticulum","Endocrinology","Phosphorylation","Population","Chemistry","Sarcoplasm","Heart failure","Serine","Biology","Ryanodine receptor","Biochemistry","ATPase","Medicine"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Gender equality"}],"linked_datasets":[{"doi":"10.6084/m9.figshare.12364523.v1","title":"Additional file 1 of Metoprolol alleviates arginine vasopressin-induced cardiomyocyte hypertrophy by upregulating the AKT1–SERCA2 cascade in H9C2 cells","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.12364523","title":"Additional file 1 of Metoprolol alleviates arginine vasopressin-induced cardiomyocyte hypertrophy by upregulating the AKT1–SERCA2 cascade in H9C2 cells","publisher":"figshare","resource_type":"JournalArticle"}],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-15T22:59:13.118400Z","pmid":null,"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":[]}