{"doi":"10.3389/fcvm.2021.792180","title":"A Link Between Methylglyoxal and Heart Failure During HIV-1 Infection","abstract":"Early-onset heart failure (HF) continues to be a major cause of morbidity and mortality in people living with human immunodeficiency virus type one (HIV-1) infection (PLWH), yet the molecular causes for this remain poorly understood. Herein NOD.Cg-Prkdc scid Il2rg tm1Wjl /SzJ humanized mice (Hu-mice), plasma from PLWH, and autopsied cardiac tissues from deceased HIV seropositive individuals were used to assess if there is a link between the glycolysis byproduct methylglyoxal (MG) and HF in the setting of HIV-1 infection. At five weeks post HIV infection, Hu-mice developed grade III-IV diastolic dysfunction (DD) with an associated two-fold increase in plasma MG. At sixteen-seventeen weeks post infection, cardiac ejection fraction and fractional shortening also declined by 26 and 35%, and plasma MG increased to four-fold higher than uninfected controls. Histopathological and biochemical analyses of cardiac tissues from Hu-mice 17 weeks post-infection affirmed MG increase with a concomitant decrease in expression of the MG-degrading enzyme glyoxalase-1 (Glo1). The endothelial cell marker CD31 was found to be lower, and coronary microvascular leakage and myocardial fibrosis were prominent. Increasing expression of Glo1 in Hu-mice five weeks post-infection using a single dose of an engineered AAV2/9 (1.7 × 10 12 virion particles/kg), attenuated the increases in plasma and cardiac MG levels. Increasing Glo1 also blunted microvascular leakage, fibrosis, and HF seen at sixteen weeks post-infection, without changes in plasma viral loads. In plasma from virally suppressed PLWH, MG was also 3.7-fold higher. In autopsied cardiac tissues from seropositive, HIV individuals with low viral log, MG was 4.2-fold higher and Glo1 was 50% lower compared to uninfected controls. These data show for the first time a causal link between accumulation of MG and HF in the setting of HIV infection.","journal":"Frontiers in Cardiovascular Medicine","year":2021,"id":185362,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9635,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":388570,"name":"Fadhel A. Alomar","orcid":"0000-0003-0788-6919","position":1,"is_corresponding":false},{"id":255898,"name":"Jesse L. Cox","orcid":"0000-0002-4590-7381","position":2,"is_corresponding":false},{"id":416455,"name":"JoEllyn McMillan","orcid":"0000-0001-6896-5122","position":3,"is_corresponding":false},{"id":284730,"name":"Bryan T. Hackfort","orcid":"0000-0002-8472-3622","position":4,"is_corresponding":false},{"id":396714,"name":"Edward Makarov","orcid":null,"position":5,"is_corresponding":false},{"id":468409,"name":"Brenda Morsey","orcid":null,"position":6,"is_corresponding":false},{"id":69464,"name":"Howard S. Fox","orcid":"0000-0003-2032-374X","position":7,"is_corresponding":false},{"id":109790,"name":"Howard E. Gendelman","orcid":"0000-0002-7831-0370","position":8,"is_corresponding":false},{"id":236489,"name":"Santhi Gorantla","orcid":"0000-0002-9064-1084","position":9,"is_corresponding":false},{"id":388572,"name":"Keshore R. Bidasee","orcid":"0000-0003-4165-8362","position":10,"is_corresponding":false},{"id":388569,"name":"Prasanta K. Dash","orcid":"0000-0002-8250-2359","position":0,"is_corresponding":true}],"reference_count":77,"raw_metadata":null,"created_at":"2026-07-18T23:48:38.805613Z","pmid":"34970611","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":[]}