A traditional Chinese medicine, Lujiao prescription, as a potential therapy for hypertrophic cardiomyocytes by acting on histone acetylation.
BACKGROUND
Chronic heart failure (CHF) is a complex clinical syndrome, and a serious stage of various heart diseases. Dysfunction of histone acetylation is involved in pathogenesis of CHF. Lujiao is a clinical and traditional prescription that has been previously used in the treatment of heart failure. The objective of our study was to explore the effects of traditional Chinese Medicine intervention with Lujiao prescription on hypertrophic cardiomyocytes with histone acetylation abnormality.


METHODS
Myocardial cells from neonatal rats were stimulated via phenylephrine (PE) and then randomly divided into seven groups: normal group (without any treatment), model group (treated with saline), TSA group (treated with trichostatin A), perindopril group (treated with perindopril), and the high, medium, and low dose of Lujiao groups (treated with 2.4 g/mL, 1.2 g/mL, and 0.6 g/mL of Lujiao, respectively). The test drug of perindopril group or Lujiao group was derived from serum after drug treatment in rats. Real-time polymerase chain reaction and Western blot were performed to analyze expression of myocyte enhancer factor 2 (MEF-2), α-major histocompatibility complex (MHC), and β-MHC and acetylation level of histone H3.


RESULTS
Expressions of MEF-2 and β-MHC were significantly increased after PE treatment and decreased after drug treatment. Expression of α-MHC mRNA was significantly reduced after PE treatment and increased after being treated with Lujiao prescription, perindopril, and TSA. The acetylation level of histone H3 decreased in rat myocardial cells stimulated by PE 48 for hours and this decrease was reversed after treatment with high and medium doses of Lujiao prescription, perindopril and TSA.


CONCLUSIONS
Histone acetylation-MEF-2-α-MHC/β-MHC axis was discovered in myocardial hypertrophy, and intervention of Lujiao prescription exhibited good effects.
Department of Cardiovascular Medicine, Shanghai Shuguang Hospital Affiliated with Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Wei
W
Zhao
Department of Cardiovascular Medicine, Shanghai Shuguang Hospital Affiliated with Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Wangying
W
Hu
Department of Cardiovascular Medicine, Shanghai Shuguang Hospital Affiliated with Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Xiaolong
X
Wang
Department of Cardiovascular Medicine, Shanghai Shuguang Hospital Affiliated with Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Nan
N
Xia
Department of Cardiovascular Medicine, Shanghai Shuguang Hospital Affiliated with Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Qixiang
Q
Hu
Department of Cardiovascular Medicine, Shanghai Shuguang Hospital Affiliated with Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address: HuaZhoutr@163.com.
Hua
H
Zhou
D000107:Acetylation; D000818:Animals; D006332:Cardiomegaly / Q000188:drug therapy*; D002478:Cells, Cultured; D006657:Histones / Q000378:metabolism*; D006877:Hydroxamic Acids / Q000627:therapeutic use; D064326:MEF2 Transcription Factors / Q000502:physiology; D008297:Male; D008516:Medicine, Chinese Traditional; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology*; D018995:Myosin Heavy Chains / Q000235:genetics; D020913:Perindopril / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley
D006657:Histones; D006877:Hydroxamic Acids; D064326:MEF2 Transcription Factors; C012589:trichostatin A; D018995:Myosin Heavy Chains; D020913:Perindopril
Lujiao prescription; histone acetylation; intervention; myocardial hypertrophy; myocyte enhancer factor 2