{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T22:34:11Z","timestamp":1790894051480,"version":"4.1.0"},"reference-count":53,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2013,11,18]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              The enzyme hexokinase\u20102 (\n              <jats:styled-content style=\"fixed-case\">HK<\/jats:styled-content>\n              2) phosphorylates glucose, which is the initiating step in virtually all glucose utilization pathways. Cardiac hypertrophy is associated with a switch towards increased glucose metabolism and decreased fatty acid metabolism. Recent evidence suggests that the increased glucose utilization is compensatory to the down\u2010regulated fatty acid metabolism during hypertrophy and is, in fact, beneficial. Therefore, we hypothesized that increasing glucose utilization by\n              <jats:styled-content style=\"fixed-case\">HK<\/jats:styled-content>\n              2 overexpression would decrease cardiac hypertrophy.\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              Mice with cardiac\u2010specific\n              <jats:styled-content style=\"fixed-case\">HK<\/jats:styled-content>\n              2 overexpression displayed decreased hypertrophy in response to isoproterenol. Neonatal rat ventricular myocytes (\n              <jats:styled-content style=\"fixed-case\">NRVM<\/jats:styled-content>\n              s) infected with an\n              <jats:styled-content style=\"fixed-case\">HK<\/jats:styled-content>\n              2 adenovirus similarly displayed decreased hypertrophy in response to phenylephrine. Hypertrophy increased reactive oxygen species (ROS) levels, which were attenuated by\n              <jats:styled-content style=\"fixed-case\">HK<\/jats:styled-content>\n              2 overexpression, thereby decreasing\n              <jats:styled-content style=\"fixed-case\">NRVM<\/jats:styled-content>\n              hypertrophy and death.\n              <jats:styled-content style=\"fixed-case\">HK<\/jats:styled-content>\n              2 appears to modulate\n              <jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content>\n              via the pentose phosphate pathway, as inhibition of glucose\u20106\u2010phosphate dehydrogenase with dehydroepiandrosterone decreased the ability of\n              <jats:styled-content style=\"fixed-case\">HK<\/jats:styled-content>\n              2 to diminish\n              <jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content>\n              and hypertrophy.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              These results suggest that\n              <jats:styled-content style=\"fixed-case\">HK<\/jats:styled-content>\n              2 attenuates cardiac hypertrophy by decreasing\n              <jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content>\n              accumulation via increased pentose phosphate pathway flux.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.113.000355","type":"journal-article","created":{"date-parts":[[2013,11,5]],"date-time":"2013-11-05T03:35:20Z","timestamp":1383622520000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":68,"title":["Cardiac\u2010specific Hexokinase 2 Overexpression Attenuates Hypertrophy by Increasing Pentose Phosphate Pathway Flux"],"prefix":"10.1161","volume":"2","author":[{"given":"Kyle 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