{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T16:08:05Z","timestamp":1792858085419,"version":"4.5.0"},"reference-count":42,"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":[[2021,6,15]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">The opening of mitochondrial permeability transition pore and inflammation cooperatively progress myocardial ischemia\u2010reperfusion (IR) injury, which hampers therapeutic effects of primary reperfusion therapy for acute myocardial infarction. We examined the therapeutic effects of nanoparticle\u2010mediated medicine that simultaneously targets mitochondrial permeability transition pore and inflammation during IR injury.<\/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 used mice lacking cyclophilin D (CypD, a key molecule for mitochondrial permeability transition pore opening) and C\u2010C chemokine receptor 2 and found that CypD contributes to the progression of myocardial IR injury at early time point (30\u201345\u00a0minutes) after reperfusion, whereas C\u2010C chemokine receptor 2 contributes to IR injury at later time point (45\u201360\u00a0minutes) after reperfusion. Double deficiency of CypD and C\u2010C chemokine receptor 2 enhanced cardioprotection compared with single deficiency regardless of the durations of ischemia. Deletion of C\u2010C chemokine receptor 2, but not deletion of CypD, decreased the recruitment of Ly\u20106C\n                      <jats:sup>high<\/jats:sup>\n                      monocytes after myocardial IR injury. In CypD\u2010knockout mice, administration of interleukin\u20101\u03b2 blocking antibody reduced the recruitment of these monocytes. Combined administration of polymeric nanoparticles composed of poly\u2010lactic\/glycolic acid and encapsulating nanoparticles containing cyclosporine A or pitavastatin, which inhibit mitochondrial permeability transition pore opening and monocyte\u2010mediated inflammation, respectively, augmented the cardioprotection as compared with single administration of nanoparticles containing cyclosporine A or pitavastatin after myocardial IR 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\">Nanoparticle\u2010mediated simultaneous targeting of mitochondrial injury and inflammation could be a novel therapeutic strategy for the treatment of myocardial IR injury.<\/jats:p>\n                  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