{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:48:00Z","timestamp":1790084880430,"version":"4.0.1"},"reference-count":196,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T00:00:00Z","timestamp":1744070400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health (NIH)","award":["R56HL151602-01A1"],"award-info":[{"award-number":["R56HL151602-01A1"]}]},{"name":"National Institutes of Health (NIH)","award":["1R01HL164306-01"],"award-info":[{"award-number":["1R01HL164306-01"]}]},{"name":"National Institutes of Health (NIH)","award":["R21NS139920-01"],"award-info":[{"award-number":["R21NS139920-01"]}]},{"name":"National Institutes of Health (NIH)","award":["37-5160-2001-011"],"award-info":[{"award-number":["37-5160-2001-011"]}]},{"name":"Neuroscience Alliance Award","award":["R56HL151602-01A1"],"award-info":[{"award-number":["R56HL151602-01A1"]}]},{"name":"Neuroscience Alliance Award","award":["1R01HL164306-01"],"award-info":[{"award-number":["1R01HL164306-01"]}]},{"name":"Neuroscience Alliance Award","award":["R21NS139920-01"],"award-info":[{"award-number":["R21NS139920-01"]}]},{"name":"Neuroscience Alliance Award","award":["37-5160-2001-011"],"award-info":[{"award-number":["37-5160-2001-011"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>People living with HIV (PLWH) develop cardiovascular diseases (CVDs) about a decade earlier and at rates 2\u20133 times higher than the general population. At present, pharmacological strategies to delay the onset of CVDs in PLWH are unavailable, in part because of an incomplete understanding of its molecular causes. We and others recently uncovered elevated levels of the toxic glycolysis and inflammation-induced byproduct methylglyoxal (MG) in plasma from PLWH and from HIV-infected humanized mice (Hu-mice). We also found a reduction in expression of the primary MG-degrading enzyme glyoxalase I (Glo-I) in autopsied cardiac tissues from HIV-1-infected individuals and HIV-1-infected Hu-mice. Increasing the expression of Glo-I in HIV-1-infected Hu-mice not only attenuated heart failure but also reduced endothelial cell damage, increased the density of perfused microvessels, prevented microvascular leakage and micro-ischemia, and blunted the expression of the inflammation-induced protein vascular protein-1 (VAP-1), key mediators of CVDs. In this narrative review, we posit that elevated MG is a contributing cause for the early onset of CVDs in PLWH. Pharmacological strategies to prevent MG accumulation and delay the development of early-onset CVDs in PLWH are also discussed.<\/jats:p>","DOI":"10.3390\/v17040547","type":"journal-article","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T07:49:02Z","timestamp":1744184942000},"page":"547","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Elevated Methylglyoxal: An Elusive Risk Factor Responsible for Early-Onset Cardiovascular Diseases in People Living with HIV-1 Infection"],"prefix":"10.3390","volume":"17","author":[{"given":"Mahendran","family":"Ramasamy","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68130, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8073-5094","authenticated-orcid":false,"given":"Zachary L.","family":"Venn","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68130, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0788-6919","authenticated-orcid":false,"given":"Fadhel A.","family":"Alomar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6490-2463","authenticated-orcid":false,"given":"Ali","family":"Namvaran","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68130, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benson","family":"Edagwa","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68130, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santhi","family":"Gorantla","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68130, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4165-8362","authenticated-orcid":false,"given":"Keshore R.","family":"Bidasee","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68130, USA"},{"name":"Environment and Occupational Health, University of Nebraska Medical Center, Omaha, NE 68198, USA"},{"name":"Nebraska Redox Biology Center, Lincoln, NE 68503, USA"},{"name":"Center for Heart and Vascular Research, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Frescura, L., Godfrey-Faussett, P., Feizzadeh, A., El-Sadr, W., Syarif, O., Ghys, P.D., and on and behalf of the 2025 testing treatment target Working Group (2022). 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