PMID- 27578362
OWN - NLM
STAT- MEDLINE
DCOM- 20170630
LR  - 20170817
IS  - 1869-1889 (Electronic)
IS  - 1674-7305 (Linking)
VI  - 59
IP  - 11
DP  - 2016 Nov
TI  - Human paraoxonase gene cluster overexpression alleviates angiotensin II-induced 
      cardiac hypertrophy in mice.
PG  - 1115-1122
AB  - Cardiac hypertrophy is the strongest predictor of the development of heart 
      failure, and anti-hypertrophic treatment holds the key to improving the clinical 
      syndrome and increasing the survival rates for heart failure. The paraoxonase 
      (PON) gene cluster (PC) protects against atherosclerosis and coronary artery 
      diseases. However, the role of PC in the heart is largely unknown. To evaluate 
      the roles of PC in cardiac hypertrophy, transgenic mice carrying the intact human 
      PON1, PON2, and PON3 genes and their flanking sequences were studied. We 
      demonstrated that the PC transgene (PC-Tg) protected mice from cardiac 
      hypertrophy induced by Ang II; these mice had reduced heart weight/body weight 
      ratios, decreased left ventricular wall thicknesses and increased fractional 
      shortening compared with wild-type (WT) control. The same protective tendency was 
      also observed with an Apoe (-/-) background. Mechanically, PC-Tg normalized the 
      disequilibrium of matrix metalloproteinases (MMPs)/tissue inhibitors of MMPs 
      (TIMPs) in hypertrophic hearts, which might contribute to the protective role of 
      PC-Tg in cardiac fibrosis and, thus, protect against cardiac remodeling. Taken 
      together, our results identify a novel anti-hypertrophic role for the PON gene 
      cluster, suggesting a possible strategy for the treatment of cardiac hypertrophy 
      through elevating the levels of the PON gene family.
FAU - Pei, Jian-Fei
AU  - Pei JF
AD  - State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and 
      Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of 
      Medical Sciences & Peking Union Medical College, Beijing, 100005, China.
FAU - Yan, Yun-Fei
AU  - Yan YF
AD  - State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and 
      Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of 
      Medical Sciences & Peking Union Medical College, Beijing, 100005, China.
FAU - Tang, Xiaoqiang
AU  - Tang X
AD  - State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and 
      Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of 
      Medical Sciences & Peking Union Medical College, Beijing, 100005, China.
FAU - Zhang, Yang
AU  - Zhang Y
AD  - State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and 
      Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of 
      Medical Sciences & Peking Union Medical College, Beijing, 100005, China.
FAU - Cui, Shen-Shen
AU  - Cui SS
AD  - State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and 
      Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of 
      Medical Sciences & Peking Union Medical College, Beijing, 100005, China.
FAU - Zhang, Zhu-Qin
AU  - Zhang ZQ
AD  - State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and 
      Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of 
      Medical Sciences & Peking Union Medical College, Beijing, 100005, China.
FAU - Chen, Hou-Zao
AU  - Chen HZ
AD  - State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and 
      Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of 
      Medical Sciences & Peking Union Medical College, Beijing, 100005, China. 
      chenhouzao@ibms.cams.cn.
FAU - Liu, De-Pei
AU  - Liu DP
AD  - State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and 
      Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of 
      Medical Sciences & Peking Union Medical College, Beijing, 100005, China. 
      liudp@pumc.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20160830
PL  - China
TA  - Sci China Life Sci
JT  - Science China. Life sciences
JID - 101529880
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - 11128-99-7 (Angiotensin II)
RN  - EC 3.1.8.1 (Aryldialkylphosphatase)
RN  - EC 3.1.8.1 (PON1 protein, human)
RN  - EC 3.1.8.1 (PON2 protein, human)
RN  - EC 3.1.8.1 (PON3 protein, human)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Angiotensin II
MH  - Animals
MH  - Aryldialkylphosphatase/genetics/*metabolism
MH  - Blood Pressure/genetics
MH  - Blotting, Western
MH  - Cardiomegaly/chemically induced/*enzymology/genetics
MH  - Echocardiography
MH  - Fibrosis/enzymology/genetics
MH  - Gene Expression Regulation, Enzymologic
MH  - Heart/physiopathology
MH  - Humans
MH  - Male
MH  - Matrix Metalloproteinases/metabolism
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Multigene Family
MH  - Myocardium/enzymology/metabolism/pathology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Tissue Inhibitor of Metalloproteinases/metabolism
MH  - Ventricular Remodeling/genetics
OTO - NOTNLM
OT  - angiotensin II
OT  - cardiac hypertrophy
OT  - fibrosis
OT  - paraoxonase gene cluster
EDAT- 2016/09/01 06:00
MHDA- 2017/07/01 06:00
CRDT- 2016/09/01 06:00
PHST- 2016/05/17 00:00 [received]
PHST- 2016/06/21 00:00 [accepted]
PHST- 2016/09/01 06:00 [pubmed]
PHST- 2017/07/01 06:00 [medline]
PHST- 2016/09/01 06:00 [entrez]
AID - 10.1007/s11427-016-0131-4 [pii]
AID - 10.1007/s11427-016-0131-4 [doi]
PST - ppublish
SO  - Sci China Life Sci. 2016 Nov;59(11):1115-1122. doi: 10.1007/s11427-016-0131-4. 
      Epub 2016 Aug 30.