{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T16:59:26Z","timestamp":1785257966517,"version":"3.55.0"},"reference-count":87,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"14","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,7,21]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Heart failure is associated with the accumulation of reactive lipid peroxidation\u2010derived aldehydes, such as acrolein, which form immunogenic protein adducts in the heart. Histidyl dipeptides, including carnosine (\u03b2\u2010alanine\u2010histidine), can covalently sequester these aldehydes. We tested whether increasing myocardial carnosine through \u03b2\u2010alanine supplementation reduces aldehyde stress, limits the immunogenicity of aldehyde\u2010modified proteins, and improves cardiac function during pressure overload\u2010induced heart failure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Male, wild\u2010type C57BL\/6J mice underwent sham or transverse aortic constriction (TAC) surgery. \u03b2\u2010alanine was administered in drinking water either before TAC or beginning 4\u2009weeks after TAC and continued for the remainder of the study. Cardiac function was evaluated by echocardiography. Myocardial histidyl dipeptides and aldehyde\u2010dipeptide conjugates were quantified by liquid chromatography with tandem mass spectrometry, and immune cell populations and CD4\n                      <jats:sup>+<\/jats:sup>\n                      T\u2010cell activation were evaluated by flow cytometry.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Myocardial carnosine and anserine levels were decreased at 3 and 8\u2009weeks after TAC. \u03b2\u2010alanine administered either before or after TAC increased myocardial histidyl dipeptide levels, attenuated pathological cardiac remodeling and fibrosis, and reduced protein carbonylation in failing hearts. Carnosine binding to aldehyde\u2010modified proteins decreased their antigenic potential. In\u00a0vitro, this reduced dendritic cell activation and CD4\n                      <jats:sup>+<\/jats:sup>\n                      T\u2010cell responses. In\u00a0vivo, \u03b2\u2010alanine pretreatment reduced the cardiac infiltration of CD4\n                      <jats:sup>+<\/jats:sup>\n                      CD44\n                      <jats:sup>+<\/jats:sup>\n                      effector T cells and CD11b\n                      <jats:sup>+<\/jats:sup>\n                      CD64\n                      <jats:sup>\u2212<\/jats:sup>\n                      Ly6G\n                      <jats:sup>+<\/jats:sup>\n                      neutrophils.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Increasing myocardial carnosine mitigates aldehyde stress, reduces the immunogenicity of aldehyde modified proteins and limits maladaptive immune responses, thereby preserving cardiac function during pressure overload. These findings support \u03b2\u2010alanine supplementation as a potential therapeutic strategy to attenuate inflammation and improve outcomes in heart failure.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.125.047630","type":"journal-article","created":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T03:25:33Z","timestamp":1783740333000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Carnosinylation of Cardiac Antigens Attenuates Immunogenic Responses and Improves Function in Failing Hearts"],"prefix":"10.1161","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9408-1304","authenticated-orcid":false,"given":"Benjamin","family":"Doelling","sequence":"first","affiliation":[{"name":"Center for Cardiometabolic Science","place":["Louisville, USA"]},{"name":"University of Louisville School of Medicine","place":["Louisville, 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