Targeted cardiac overexpression of A20 improves left ventricular performance and reduces compensatory hypertrophy after myocardial infarction

Hong Liang Li, Ming Lei Zhuo, Dong Wang, Ai Bing Wang, Hua Cai, Li Hong Sun, Qinglin Yang, Yue Huang, Yu Sheng Wei, Peter P. Liu, De Pei Liu, Chih Chuan Liang

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Abstract

BACKGROUND - A20 was originally characterized as a tumor necrosis factor-inducible gene in human umbilical vein endothelial cells. As an inhibitor of nuclear factor-κB signaling, A20 protects against apoptosis, inflammation, and cardiac hypertrophy. In the present study, we tested the hypothesis that cardiac-specific overexpression of A20 could protect the heart from myocardial infarction. METHODS AND RESULTS - We investigated the role of constitutive human A20 expression in acute myocardial infarction using a transgenic model. Transgenic mice containing the human A20 gene under the control of the α-myosin heavy chain promoter were constructed. Myocardial infarction was produced by coronary ligation in A20 transgenic mice and control animals. The extent of infarction was then quantified by 2-dimensional and M-mode echocardiography and by molecular and pathological analyses of heart samples in infarct and remote heart regions 7 days after myocardial infarction. Constitutive overexpression of A20 in the murine heart resulted in attenuated infarct size and improved cardiac function 7 days after myocardial infarction. Significantly, we found a decrease in nuclear factor-κB signaling and apoptosis, as well as proinflammatory response, cardiac remodeling, and interstitial fibrosis, in noninfarct regions in the hearts of constitutive A20-expressing animals compared with control animals. CONCLUSIONS - Cardiac-specific overexpression of A20 improves cardiac function and inhibits cardiac remodeling, apoptosis, inflammation, and fibrosis after acute myocardial infarction.

Original languageEnglish (US)
Pages (from-to)1885-1894
Number of pages10
JournalCirculation
Volume115
Issue number14
DOIs
StatePublished - Apr 1 2007

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Hypertrophy
Myocardial Infarction
Apoptosis
Transgenic Mice
Fibrosis
Inflammation
Myosin Heavy Chains
Human Umbilical Vein Endothelial Cells
Cardiomegaly
Infarction
Genes
Ligation
Echocardiography
Tumor Necrosis Factor-alpha

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Targeted cardiac overexpression of A20 improves left ventricular performance and reduces compensatory hypertrophy after myocardial infarction. / Li, Hong Liang; Zhuo, Ming Lei; Wang, Dong; Wang, Ai Bing; Cai, Hua; Sun, Li Hong; Yang, Qinglin; Huang, Yue; Wei, Yu Sheng; Liu, Peter P.; Liu, De Pei; Liang, Chih Chuan.

In: Circulation, Vol. 115, No. 14, 01.04.2007, p. 1885-1894.

Research output: Contribution to journalArticle

Li, HL, Zhuo, ML, Wang, D, Wang, AB, Cai, H, Sun, LH, Yang, Q, Huang, Y, Wei, YS, Liu, PP, Liu, DP & Liang, CC 2007, 'Targeted cardiac overexpression of A20 improves left ventricular performance and reduces compensatory hypertrophy after myocardial infarction', Circulation, vol. 115, no. 14, pp. 1885-1894. https://doi.org/10.1161/CIRCULATIONAHA.106.656835
Li, Hong Liang ; Zhuo, Ming Lei ; Wang, Dong ; Wang, Ai Bing ; Cai, Hua ; Sun, Li Hong ; Yang, Qinglin ; Huang, Yue ; Wei, Yu Sheng ; Liu, Peter P. ; Liu, De Pei ; Liang, Chih Chuan. / Targeted cardiac overexpression of A20 improves left ventricular performance and reduces compensatory hypertrophy after myocardial infarction. In: Circulation. 2007 ; Vol. 115, No. 14. pp. 1885-1894.
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AU - Huang, Yue

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