Histone deacetylase inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in DOCA-induced hypertensive rats.
CG200745 is a novel inhibitor of histone deacetylases (HDACs), initially developed for treatment of various hematological and solid cancers. Because it is water-soluble, it can be administered orally. We hypothesized that the HDAC inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in deoxycorticosterone acetate (DOCA)-induced hypertensive rats. For establishment of hypertension, 40 mg/kg of DOCA was subcutaneously injected four times weekly into Sprague-Dawley rats. All the rats used in this study including those in the sham group had been unilaterally nephrectomized and allowed free access to drinking water containing 1% NaCl. Systolic blood pressure was measured by the tail-cuff method. Blood chemistry including sodium, potassium, glucose, triglyceride, and cholesterol levels was analyzed. Sections of the heart were visualized after trichrome and hematoxylin and eosin stain. The expression of hypertrophic genes such as atrial natriuretic peptide A (Nppa) and atrial natriuretic peptide B (Nppb) in addition to fibrotic genes such as Collagen-1, Collagen-3, connective tissue growth factor (Ctgf), and Fibronectin were measured by quantitative real-time PCR (qRT-PCR). Injection of DOCA increased systolic blood pressure, heart weight, and cardiac fibrosis, which was attenuated by CG200745. Neither DOCA nor CG200745 affected body weight, vascular contraction and relaxation responses, and blood chemistry. Injection of DOCA increased expression of both hypertrophic and fibrotic genes, which was abrogated by CG200745. These results indicate that CG200745 attenuates cardiac hypertrophy and fibrosis in DOCA-induced hypertensive rats.
Department of Pharmacology, Kyungpook National University School of Medicine, Daegu 41944, Korea.; Cardiovascular Research Institute, Kyungpook National University School of Medicine, Daegu 41944, Korea.; Cell and Matrix Research Institute, Kyungpook National University School of Medicine, Daegu 41944, Korea.; BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University School of Medicine, Daegu 41944, Korea.
Eunjo
E
Lee
Department of Pharmacology, Kyungpook National University School of Medicine, Daegu 41944, Korea.
Min-Ji
MJ
Song
Department of Pharmacology, Kyungpook National University School of Medicine, Daegu 41944, Korea.; Cardiovascular Research Institute, Kyungpook National University School of Medicine, Daegu 41944, Korea.; Cell and Matrix Research Institute, Kyungpook National University School of Medicine, Daegu 41944, Korea.
Hae-Ahm
HA
Lee
Department of Pharmacology, Kyungpook National University School of Medicine, Daegu 41944, Korea.; Cardiovascular Research Institute, Kyungpook National University School of Medicine, Daegu 41944, Korea.; Cell and Matrix Research Institute, Kyungpook National University School of Medicine, Daegu 41944, Korea.; BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University School of Medicine, Daegu 41944, Korea.
Seol-Hee
SH
Kang
Department of Pharmacology, Kyungpook National University School of Medicine, Daegu 41944, Korea.; Cardiovascular Research Institute, Kyungpook National University School of Medicine, Daegu 41944, Korea.; Cell and Matrix Research Institute, Kyungpook National University School of Medicine, Daegu 41944, Korea.; BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University School of Medicine, Daegu 41944, Korea.
Mina
M
Kim
Department of Physiology, Kyungpook National University School of Medicine, Daegu 41944, Korea.
Eun Kyoung
EK
Yang
Translational Research Center, CrystalGenomics, Inc., Seongnam 13488, Korea.
Do Young
do Y
Lee
Translational Research Center, CrystalGenomics, Inc., Seongnam 13488, Korea.
Seonggu
S
Ro
Translational Research Center, CrystalGenomics, Inc., Seongnam 13488, Korea.
Joong Myung
JM
Cho
Department of Pharmacology, Kyungpook National University School of Medicine, Daegu 41944, Korea.; Cardiovascular Research Institute, Kyungpook National University School of Medicine, Daegu 41944, Korea.; Cell and Matrix Research Institute, Kyungpook National University School of Medicine, Daegu 41944, Korea.; BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University School of Medicine, Daegu 41944, Korea.
Inkyeom
I
Kim
CG200745; Cardiac fibrosis; Cardiac hypertrophy; Deoxycorticosterone acetate (DOCA); Histone deacetylase