{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T06:17:47Z","timestamp":1788329867642,"version":"build-2803163510"},"reference-count":58,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"17","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Left ventricular (LV) reverse remodeling has been linked to long\u2010term prognosis and life quality of pediatric patients with LV outflow tract obstruction. However, a lack of suitable animal model limits further study of LV reverse remodeling in young hearts. This study reports on the development and mechanism exploration of an animal model mimicking pediatric LV reverse remodeling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">A reversible neonatal ascending aorta constriction mice model using absorbable suture was established to simulate pediatric LV reverse remodeling. Cardiac hypertrophy, myocardial fibrosis, angiogenesis, exercise tolerance, and myocardial reserve throughout the reverse remodeling process were evaluated. Multiple\u2010time points RNA sequencing identified key genes and pathways involved. Cardiomyocyte\u2010specific stimulator of interferon genes (STING)\u00a0knockout mice were generated for mechanism study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">In the reversible neonatal ascending aorta constriction model, hydrolysis of the absorbable suture reduced cardiac afterload after ventricular remodeling, initiating reverse remodeling at 4\u2009weeks postsurgery. Reverse remodeling young hearts displayed improved function, resolution of fibrosis, but persistent hypertrophy, reduced exercise capacity, and myocardial reserve. Multiple\u2010time points RNA sequencing and in\u00a0vivo experiments revealed a gradual upregulation of mitophagy during reverse remodeling, along with suppression of the mitochondrial DNA (mtDNA)\u2010cyclic GMP\u2010AMP synthase (cGAS) in which the STING gene is flanked by loxP sites\u2010STING pathway. Cardiomyocyte\u2010specific STING knockout enhanced early reverse remodeling. The early application of urolithin A promoted mitophagy and suppressed the mtDNA\u2010cGAS\u2010STING pathway, accelerating reverse remodeling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">This study introduces a novel model of pediatric LV reverse remodeling in male mice, delineating the trajectory and transcriptional footprints during the reverse remodeling process. The Mitophagy\u2010mtDNA\u2010cGAS\u2010STING axis plays a vital role and holds therapeutic potential to promote young heart recovery.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.125.047618","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T11:17:05Z","timestamp":1787829425000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Neonatal Reversible Aortic Constriction Mice Model Unlocks Distinctive Footprints of Young Heart Recovery"],"prefix":"10.1161","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-5825-4679","authenticated-orcid":false,"given":"Longming","family":"Huang","sequence":"first","affiliation":[{"name":"Shanghai Children\u2019s Medical Center, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, 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