{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T15:30:30Z","timestamp":1790523030588,"version":"4.1.0"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Hydrogen sulfide (H\n                      <jats:sub>2<\/jats:sub>\n                      S) is a gasotransmitter that regulates multiple cardiovascular functions. Kr\u00fcppel\u2010like factor 5 (KLF5) exerts diverse functions in the cardiovascular system. Whether and how H\n                      <jats:sub>2<\/jats:sub>\n                      S regulates KLF5 in myocardial hypertrophy is unknown.\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                      In our study, hypertrophic myocardial samples in the clinic were collected and underwent histological and molecular biological analysis. Spontaneously hypertensive rats and neonatal rat cardiomyocytes were studied for functional and signaling responses to GYY4137, an H\n                      <jats:sub>2<\/jats:sub>\n                      S\u2010releasing compound. Expression of cystathionine \u03b3\u2010lyase, a principal enzyme for H\n                      <jats:sub>2<\/jats:sub>\n                      S generation in heart, decreased in human hypertrophic myocardium, whereas KLF5 expression increased. After GYY4137 administration for 4\u00a0weeks, myocardial hypertrophy was inhibited in spontaneously hypertensive rats, as demonstrated by improvement in cardiac structural parameters, heart mass, size of cardiac myocytes, and expression of atrial natriuretic peptide. H\n                      <jats:sub>2<\/jats:sub>\n                      S diminished expression of KLF5 in myocardium of spontaneously hypertensive rats and in hypertrophic cardiomyocytes. H\n                      <jats:sub>2<\/jats:sub>\n                      S also inhibits platelet\u2010derived growth factor A promoter activity, decreased recruitment of KLF5 to the platelet\u2010derived growth factor A promoter, and reduced atrial natriuretic peptide expression in angiotensin II\u2013stimulated cardiomyocytes, and these effects are suppressed by KLF5 knockdown. KLF5 promoter activity and KLF5 expression was also reversed by H\n                      <jats:sub>2<\/jats:sub>\n                      S. H\n                      <jats:sub>2<\/jats:sub>\n                      S increased the S\u2010sulfhydration on specificity protein 1 in cardiomyocytes. Moreover, H\n                      <jats:sub>2<\/jats:sub>\n                      S decreased KLF5 promoter activity; reduced KLF5 mRNA expression; attenuated specificity protein 1 binding activity with KLF5 promoter; and inhibited hypertrophy after specificity protein 1 mutated at Cys659, Cys689, and Cys692 but not Cys664 overexpression.\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 findings suggest that H\n                      <jats:sub>2<\/jats:sub>\n                      S regulates KLF5 transcription activity via specificity protein 1 S\u2010sulfhydration at Cys664 to prevent myocardial hypertrophy.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.116.004160","type":"journal-article","created":{"date-parts":[[2016,9,16]],"date-time":"2016-09-16T21:10:39Z","timestamp":1474060239000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":77,"title":["Hydrogen Sulfide Regulates Kr\u00fcppel\u2010Like Factor 5 Transcription Activity via Specificity Protein 1 S\u2010Sulfhydration at Cys664 to Prevent Myocardial Hypertrophy"],"prefix":"10.1161","volume":"5","author":[{"given":"Guoliang","family":"Meng","sequence":"first","affiliation":[{"name":"Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing, China"},{"name":"Department of Pharmacology, School of Pharmacy, Nantong University, Nantong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujiao","family":"Xiao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing, China"},{"name":"Department of Pathology, Jincheng People's Hospital, Jincheng, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Ma","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Tang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Xie","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing, 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