{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:28:18Z","timestamp":1790256498210,"version":"4.1.0"},"reference-count":70,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2019,1,8]],"date-time":"2019-01-08T00:00:00Z","timestamp":1546905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,1,8]],"date-time":"2019-01-08T00:00:00Z","timestamp":1546905600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:sec>\n                    <jats:title>Aims:<\/jats:title>\n                    <jats:p>\n                      Metabolic remodeling of cardiac muscles during pathological hypertrophy is characterized by downregulation of fatty acid oxidation (FAO) regulator, peroxisome proliferator-activated receptor alpha (\n                      <jats:italic toggle=\"yes\">PPAR\u03b1<\/jats:italic>\n                      ). Thereby, we hypothesized that a cardiac-specific induction of PPAR\u03b1 might restore the FAO-related protein expression and resultant energy deficit. In the present study, consequences of PPAR\u03b1 augmentation were evaluated for amelioration of chronic oxidative stress, myocyte apoptosis, and cardiac function during pathological cardiac hypertrophy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Nanotized PPAR\u03b1 overexpression targeted to myocardium was done by a stearic acid-modified carboxymethyl-chitosan (CMC) conjugated to a 20-mer myocyte-targeted peptide (CMCP). Overexpression of\n                      <jats:italic toggle=\"yes\">PPAR\u03b1<\/jats:italic>\n                      ameliorated pathological hypertrophy and improved cardiac function. Augmented PPAR\u03b1 in hypertrophied myocytes revealed downregulated p53 acetylation (lys 382), leading to reduced apoptosis. Such cells showed increased binding of PPAR\u03b1 with p53 that in turn reduced interaction of p53 with glycogen synthase kinase-3\u03b2 (GSK3\u03b2), which upregulated inactive phospho-GSK3\u03b2 (serine [Ser]9) expression within mitochondrial protein fraction. Altogether, the altered molecular milieu in\n                      <jats:italic toggle=\"yes\">PPAR\u03b1<\/jats:italic>\n                      -overexpressed hypertrophy groups restored mitochondrial structure and function both\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Innovation:<\/jats:title>\n                    <jats:p>\n                      Cardiomyocyte-targeted overexpression of a protein of interest (PPAR\u03b1) by nanotized plasmid has been described for the first time in this study. Our data provide a novel insight towards regression of pathological hypertrophy by ameliorating mitochondrial oxidative stress in targeted\n                      <jats:italic toggle=\"yes\">PPAR\u03b1<\/jats:italic>\n                      -overexpressed myocardium.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">PPAR\u03b1<\/jats:italic>\n                      -overexpression during pathological hypertrophy showed substantial betterment of mitochondrial structure and function, along with downregulated apoptosis. Myocardium-targeted overexpression of\n                      <jats:italic toggle=\"yes\">PPAR\u03b1<\/jats:italic>\n                      during pathological cardiac hypertrophy led to an overall improvement of cardiac energy deficit and subsequent cardiac function, thereby, opening up a potential avenue for cardiac tissue engineering during hypertrophic cardiac pathophysiology.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/ars.2017.7371","type":"journal-article","created":{"date-parts":[[2018,4,10]],"date-time":"2018-04-10T04:50:30Z","timestamp":1523335830000},"page":"713-732","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":26,"title":["Nanotized\n                    <i>PPAR\u03b1<\/i>\n                    Overexpression Targeted to Hypertrophied Myocardium Improves Cardiac Function by Attenuating the p53-GSK3\u03b2-Mediated Mitochondrial Death Pathway"],"prefix":"10.1177","volume":"30","author":[{"given":"Santanu","family":"Rana","sequence":"first","affiliation":[{"name":"Department of Zoology, University of Calcutta, Kolkata, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ritwik","family":"Datta","sequence":"additional","affiliation":[{"name":"Department of Zoology, University of Calcutta, Kolkata, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ratul Datta","family":"Chaudhuri","sequence":"additional","affiliation":[{"name":"Department of Zoology, University of Calcutta, Kolkata, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emeli","family":"Chatterjee","sequence":"additional","affiliation":[{"name":"Department of Zoology, University of Calcutta, Kolkata, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mamta","family":"Chawla-Sarkar","sequence":"additional","affiliation":[{"name":"Division of Virology, National Institute of Cholera and Enteric Diseases, Kolkata, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sagartirtha","family":"Sarkar","sequence":"additional","affiliation":[{"name":"Department of Zoology, University of Calcutta, Kolkata, India."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2019,1,8]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfm110"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.02.001"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.8.15.1739"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI9056"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2006.07.006"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00734-13"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110598200"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2010.165"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M106054200"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.217349"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.22599"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2012.05.022"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/22.24.5439"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/378785a0"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.110.232306"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvq068"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2015.09.005"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00611-16"},{"key":"e_1_3_4_20_2","first-page":"H1983","article-title":"Fenofibrate inhibits aldosterone-induced apoptosis in adult rat ventricular myocytes via stress-activated kinase-dependent mechanisms","volume":"296","author":"De Silva DS","year":"2009","unstructured":"De Silva DS, , Wilson RM, , Hutchinson C, , Ip PC, , Garcia AG, , Lancel S, , Ito M, , Pimentel DR, , and Sam F. 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