title: Phenylephrine-induced cardiac hypertrophy is attenuated by a histone acetylase inhibitor anacardic acid in mice.
abstract: Cardiac hypertrophy is a complex process involving highly coordinated but tight regulation of multiple elements, such as in epigenetics, which make an important contribution to myocardium remodeling and cardiac hypertrophy. Epigenetic regulations, particularly histone acetylation, have been implicated in cardiac hypertrophy, however, the exact mechanism is still largely unknown. In the present study, we explored the potential attenuating effects of Chinese herbal extract anacardic acid on phenylephrine-induced cardiac hypertrophy and the underlying mechanism. The mouse cardiac hypertrophy model was established and the hearts were collected from C57BL/6 mice for further analyses. The data showed that anacardic acid modulated the cardiac genes expression and attenuated the phenylephrine-induced cardiac hypertrophy via the suppression of histone acetylases activity and downstream cardiac genes. In addition, anacardic acid abrogated histone and MEF2A acetylation and DNA-binding activity by blocking p300-HAT and PCAF-HAT activities. In addition, anacardic acid normalized the cardiac hypertrophy-related genes expressions (ANP, BNP, cTnT, cTnI, β-MHC, and Cx43) induced by phenylephrine at the level of transcription and translation. In addition, anacardic acid did not affect the blood routine index, hepatic function, renal function, and myocardial enzymes. Therefore, anacardic acid may prove to be a candidate drug to cure hypertrophic cardiomyopathy.
authors.affiliation: Department of Pediatrics, Affiliated Hospital of Zunyi Medical College, Guizhou, China.
authors.forename: Chang
authors.identifier: http://orcid.org/0000-0001-7355-8337
authors.initials: C
authors.lastname: Peng
authors.affiliation: Department of Physiology, Zunyi Medical College, Guizhou, China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Luo
authors.affiliation: Department of Pediatrics, Affiliated Hospital of Zunyi Medical College, Guizhou, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Li
authors.affiliation: Heart Center, Children's Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Huichao
authors.initials: H
authors.lastname: Sun
mesh_terms: D000107:Acetylation; D048729:Anacardic Acids / Q000494:pharmacology*; D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006334:Heart Function Tests; D051548:Histone Acetyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D064326:MEF2 Transcription Factors / Q000235:genetics; D008297:Male; D051379:Mice; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010656:Phenylephrine / Q000009:adverse effects; D011485:Protein Binding; D014158:Transcription, Genetic
chemical_list: D048729:Anacardic Acids; D006657:Histones; D064326:MEF2 Transcription Factors; C088115:anacardic acid; D010656:Phenylephrine; D051548:Histone Acetyltransferases