{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T07:27:09Z","timestamp":1789457229619,"version":"build-2803163510"},"reference-count":79,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2020,6,16]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>BACKGROUND<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Myocardial ischemia reperfusion (I\/R) injury is associated with complex pathophysiological changes characterized by\n              <jats:styled-content style=\"fixed-case\">pH<\/jats:styled-content>\n              imbalance, the accumulation of lipid peroxidation products acrolein and 4\u2010hydroxy\n              <jats:italic>trans<\/jats:italic>\n              \u20102\u2010nonenal, and the depletion of\n              <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>\n              levels. Cardioprotective interventions, designed to address individual mediators of I\/R injury, have shown limited efficacy. The recently identified enzyme ATPGD1 (Carnosine Synthase), which synthesizes histidyl dipeptides such as carnosine, has the potential to counteract multiple effectors of I\/R injury by buffering intracellular\n              <jats:styled-content style=\"fixed-case\">pH<\/jats:styled-content>\n              and quenching lipid peroxidation products and may protect against I\/R injury\n              <jats:bold>.<\/jats:bold>\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>METHODS AND RESULTS<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              We report here that \u03b2\u2010alanine and carnosine feeding enhanced myocardial carnosine levels and protected the heart against I\/R injury. Cardiospecific overexpression of\n              <jats:styled-content style=\"fixed-case\">ATPGD<\/jats:styled-content>\n              1 increased myocardial histidyl dipeptides levels and protected the heart from I\/R injury. Isolated cardiac myocytes from\n              <jats:styled-content style=\"fixed-case\">ATPGD<\/jats:styled-content>\n              1\u2010transgenic hearts were protected against hypoxia reoxygenation injury. The overexpression of\n              <jats:styled-content style=\"fixed-case\">ATPGD<\/jats:styled-content>\n              1 prevented the accumulation of acrolein and 4\u2010hydroxy\n              <jats:italic>trans<\/jats:italic>\n              \u20102\u2010nonenal\u2013protein adducts in ischemic hearts and delayed acrolein or 4\u2010hydroxy\n              <jats:italic>trans<\/jats:italic>\n              \u20102\u2010nonenal\u2013induced hypercontracture in isolated cardiac myocytes. Changes in the levels of\n              <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>\n              , high\u2010energy phosphates, intracellular pH, and glycolysis during low\u2010flow ischemia in the wild\u2010type mice hearts were attenuated in the\n              <jats:styled-content style=\"fixed-case\">ATPGD<\/jats:styled-content>\n              1\u2010transgenic hearts. Two natural dipeptide analogs (anserine and balenine) that can either quench aldehydes or buffer intracellular\n              <jats:styled-content style=\"fixed-case\">pH<\/jats:styled-content>\n              , but not both, failed to protect against I\/R injury.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>CONCLUSIONS<\/jats:title>\n            <jats:p xml:lang=\"en\">Either exogenous administration or enhanced endogenous formation of histidyl dipeptides prevents I\/R injury by attenuating changes in intracellular pH and preventing the accumulation of lipid peroxidation derived aldehydes.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.119.015222","type":"journal-article","created":{"date-parts":[[2020,6,9]],"date-time":"2020-06-09T09:18:07Z","timestamp":1591694287000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":50,"title":["Cardiospecific 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