Deficiency of Ataxia Telangiectasia Mutated Kinase Modulates Cardiac Remodeling Following Myocardial Infarction: Involvement in Fibrosis and Apoptosis
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作者:
Foster, Cerrone R.
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E Tennessee State Univ, Dept Biomed Sci, James H Quillen Coll Med, James H Quillen Vet Affairs Med Ctr, Johnson City, TN 37614 USAE Tennessee State Univ, Dept Biomed Sci, James H Quillen Coll Med, James H Quillen Vet Affairs Med Ctr, Johnson City, TN 37614 USA
Foster, Cerrone R.
[1
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Daniel, Laura L.
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E Tennessee State Univ, Dept Biomed Sci, James H Quillen Coll Med, James H Quillen Vet Affairs Med Ctr, Johnson City, TN 37614 USAE Tennessee State Univ, Dept Biomed Sci, James H Quillen Coll Med, James H Quillen Vet Affairs Med Ctr, Johnson City, TN 37614 USA
Daniel, Laura L.
[1
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Daniels, Christopher R.
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E Tennessee State Univ, Dept Biomed Sci, James H Quillen Coll Med, James H Quillen Vet Affairs Med Ctr, Johnson City, TN 37614 USAE Tennessee State Univ, Dept Biomed Sci, James H Quillen Coll Med, James H Quillen Vet Affairs Med Ctr, Johnson City, TN 37614 USA
Daniels, Christopher R.
[1
]
Dalal, Suman
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E Tennessee State Univ, Dept Biomed Sci, James H Quillen Coll Med, James H Quillen Vet Affairs Med Ctr, Johnson City, TN 37614 USAE Tennessee State Univ, Dept Biomed Sci, James H Quillen Coll Med, James H Quillen Vet Affairs Med Ctr, Johnson City, TN 37614 USA
Dalal, Suman
[1
]
Singh, Mahipal
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E Tennessee State Univ, Dept Biomed Sci, James H Quillen Coll Med, James H Quillen Vet Affairs Med Ctr, Johnson City, TN 37614 USAE Tennessee State Univ, Dept Biomed Sci, James H Quillen Coll Med, James H Quillen Vet Affairs Med Ctr, Johnson City, TN 37614 USA
Singh, Mahipal
[1
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Singh, Krishna
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E Tennessee State Univ, Dept Biomed Sci, James H Quillen Coll Med, James H Quillen Vet Affairs Med Ctr, Johnson City, TN 37614 USAE Tennessee State Univ, Dept Biomed Sci, James H Quillen Coll Med, James H Quillen Vet Affairs Med Ctr, Johnson City, TN 37614 USA
Singh, Krishna
[1
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机构:
[1] E Tennessee State Univ, Dept Biomed Sci, James H Quillen Coll Med, James H Quillen Vet Affairs Med Ctr, Johnson City, TN 37614 USA
Ataxia telangiectasia mutated kinase (ATM) is a cell cycle checkpoint protein activated in response to DNA damage. We recently reported that ATM plays a protective role in myocardial remodeling following beta-adrenergic receptor stimulation. Here we investigated the role of ATM in cardiac remodeling using myocardial infarction (MI) as a model. Methods and Results: Left ventricular (LV) structure, function, apoptosis, fibrosis, and protein levels of apoptosis-and fibrosis-related proteins were examined in wild-type (WT) and ATM heterozygous knockout (hKO) mice 7 days post-MI. Infarct sizes were similar in both MI groups. However, infarct thickness was higher in hKO-MI group. Two dimensional M-mode echocardiography revealed decreased percent fractional shortening (% FS) and ejection fraction (EF) in both MI groups when compared to their respective sham groups. However, the decrease in % FS and EF was significantly greater in WT-MI vs hKO-MI. LV end systolic and diastolic diameters were greater in WT-MI vs hKO-MI. Fibrosis, apoptosis, and a-smooth muscle actin staining was significantly higher in hKO-MI vs WT-MI. MMP-2 protein levels and activity were increased to a similar extent in the infarct regions of both groups. MMP-9 protein levels were increased in the non-infarct region of WT-MI vs WT-sham. MMP-9 protein levels and activity were significantly lower in the infarct region of WT vs hKO. TIMP-2 protein levels similarly increased in both MI groups, whereas TIMP-4 protein levels were significantly lower in the infarct region of hKO group. Phosphorylation of p53 protein was higher, while protein levels of manganese superoxide dismutase were significantly lower in the infarct region of hKO vs WT. In vitro, inhibition of ATM using KU-55933 increased oxidative stress and apoptosis in cardiac myocytes.
机构:
Columbia Univ, Ctr Radiol Res, Coll Phys & Surg, New York, NY 10032 USAColumbia Univ, Ctr Radiol Res, Coll Phys & Surg, New York, NY 10032 USA
Ivanov, Vladimir N.
Zhou, Hongning
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Columbia Univ, Ctr Radiol Res, Coll Phys & Surg, New York, NY 10032 USAColumbia Univ, Ctr Radiol Res, Coll Phys & Surg, New York, NY 10032 USA
Zhou, Hongning
Partridge, Michael A.
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Columbia Univ, Ctr Radiol Res, Coll Phys & Surg, New York, NY 10032 USAColumbia Univ, Ctr Radiol Res, Coll Phys & Surg, New York, NY 10032 USA
Partridge, Michael A.
Hei, Tom K.
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Columbia Univ, Ctr Radiol Res, Coll Phys & Surg, New York, NY 10032 USA
Columbia Univ, Dept Environm Hlth Sci, New York, NY 10032 USAColumbia Univ, Ctr Radiol Res, Coll Phys & Surg, New York, NY 10032 USA
机构:
Univ Helsinki, Div Pharmacol & Pharmacotherapy, Fac Pharm, POB 56, FI-00014 Helsinki, FinlandUniv Helsinki, Div Pharmacol & Pharmacotherapy, Fac Pharm, POB 56, FI-00014 Helsinki, Finland
Talman, Virpi
Ruskoaho, Heikki
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Univ Helsinki, Div Pharmacol & Pharmacotherapy, Fac Pharm, POB 56, FI-00014 Helsinki, FinlandUniv Helsinki, Div Pharmacol & Pharmacotherapy, Fac Pharm, POB 56, FI-00014 Helsinki, Finland
机构:
Zhejiang Univ, Sir Run Run Shaw Hosp, Dept Cardiol, Sch Med, 3 East Qingchun Rd, Hangzhou 310016, Zhejiang, Peoples R China
Key Lab Cardiovasc Intervent & Regenerat Med Zhej, Hangzhou, Peoples R ChinaZhejiang Univ, Sir Run Run Shaw Hosp, Dept Cardiol, Sch Med, 3 East Qingchun Rd, Hangzhou 310016, Zhejiang, Peoples R China
Wang, Jiacheng
Xue, Zhimin
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Zhejiang Univ, Sir Run Run Shaw Hosp, Dept Cardiol, Sch Med, 3 East Qingchun Rd, Hangzhou 310016, Zhejiang, Peoples R China
Key Lab Cardiovasc Intervent & Regenerat Med Zhej, Hangzhou, Peoples R ChinaZhejiang Univ, Sir Run Run Shaw Hosp, Dept Cardiol, Sch Med, 3 East Qingchun Rd, Hangzhou 310016, Zhejiang, Peoples R China
Xue, Zhimin
Lin, Jun
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Zhejiang Univ, Sir Run Run Shaw Hosp, Dept Cardiol, Sch Med, 3 East Qingchun Rd, Hangzhou 310016, Zhejiang, Peoples R China
Key Lab Cardiovasc Intervent & Regenerat Med Zhej, Hangzhou, Peoples R ChinaZhejiang Univ, Sir Run Run Shaw Hosp, Dept Cardiol, Sch Med, 3 East Qingchun Rd, Hangzhou 310016, Zhejiang, Peoples R China
Lin, Jun
Wang, Yao
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Zhejiang Univ, Sir Run Run Shaw Hosp, Dept Cardiol, Sch Med, 3 East Qingchun Rd, Hangzhou 310016, Zhejiang, Peoples R China
Key Lab Cardiovasc Intervent & Regenerat Med Zhej, Hangzhou, Peoples R ChinaZhejiang Univ, Sir Run Run Shaw Hosp, Dept Cardiol, Sch Med, 3 East Qingchun Rd, Hangzhou 310016, Zhejiang, Peoples R China
Wang, Yao
Ying, Hangying
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Zhejiang Univ, Sir Run Run Shaw Hosp, Dept Cardiol, Sch Med, 3 East Qingchun Rd, Hangzhou 310016, Zhejiang, Peoples R China
Key Lab Cardiovasc Intervent & Regenerat Med Zhej, Hangzhou, Peoples R ChinaZhejiang Univ, Sir Run Run Shaw Hosp, Dept Cardiol, Sch Med, 3 East Qingchun Rd, Hangzhou 310016, Zhejiang, Peoples R China
Ying, Hangying
Lv, Qingbo
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Zhejiang Univ, Sir Run Run Shaw Hosp, Dept Cardiol, Sch Med, 3 East Qingchun Rd, Hangzhou 310016, Zhejiang, Peoples R China
Key Lab Cardiovasc Intervent & Regenerat Med Zhej, Hangzhou, Peoples R ChinaZhejiang Univ, Sir Run Run Shaw Hosp, Dept Cardiol, Sch Med, 3 East Qingchun Rd, Hangzhou 310016, Zhejiang, Peoples R China
Lv, Qingbo
Hua, Chunting
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Key Lab Biotherapy Zhejiang Prov, Hangzhou, Peoples R ChinaZhejiang Univ, Sir Run Run Shaw Hosp, Dept Cardiol, Sch Med, 3 East Qingchun Rd, Hangzhou 310016, Zhejiang, Peoples R China
Hua, Chunting
Wang, Meihui
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Zhejiang Univ, Sir Run Run Shaw Hosp, Dept Cardiol, Sch Med, 3 East Qingchun Rd, Hangzhou 310016, Zhejiang, Peoples R China
Key Lab Cardiovasc Intervent & Regenerat Med Zhej, Hangzhou, Peoples R ChinaZhejiang Univ, Sir Run Run Shaw Hosp, Dept Cardiol, Sch Med, 3 East Qingchun Rd, Hangzhou 310016, Zhejiang, Peoples R China
Wang, Meihui
Chen, Siji
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Key Lab Biotherapy Zhejiang Prov, Hangzhou, Peoples R ChinaZhejiang Univ, Sir Run Run Shaw Hosp, Dept Cardiol, Sch Med, 3 East Qingchun Rd, Hangzhou 310016, Zhejiang, Peoples R China
Chen, Siji
Zhou, Binquan
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Zhejiang Univ, Sir Run Run Shaw Hosp, Dept Cardiol, Sch Med, 3 East Qingchun Rd, Hangzhou 310016, Zhejiang, Peoples R China
Key Lab Cardiovasc Intervent & Regenerat Med Zhej, Hangzhou, Peoples R ChinaZhejiang Univ, Sir Run Run Shaw Hosp, Dept Cardiol, Sch Med, 3 East Qingchun Rd, Hangzhou 310016, Zhejiang, Peoples R China
机构:
Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Div Gastroenterol, Wuhan, Hubei, Peoples R China
Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Clin Ctr Human Gene Res, Wuhan, Hubei, Peoples R ChinaHuazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Div Gastroenterol, Wuhan, Hubei, Peoples R China
Wang, Yilong
Ju, Chenhui
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Chinese Acad Sci, Inst Biophys, Key Lab Prot & Peptide Pharmaceut, Beijing 100101, Peoples R ChinaHuazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Div Gastroenterol, Wuhan, Hubei, Peoples R China
Ju, Chenhui
Hu, Ji
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Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Clin Ctr Human Gene Res, Wuhan, Hubei, Peoples R China
Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Cardiol, Wuhan, Hubei, Peoples R ChinaHuazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Div Gastroenterol, Wuhan, Hubei, Peoples R China
Hu, Ji
Huang, Kai
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Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Clin Ctr Human Gene Res, Wuhan, Hubei, Peoples R China
Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Cardiol, Wuhan, Hubei, Peoples R ChinaHuazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Div Gastroenterol, Wuhan, Hubei, Peoples R China
Huang, Kai
Yang, Ling
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Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Div Gastroenterol, Wuhan, Hubei, Peoples R China
Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Clin Ctr Human Gene Res, Wuhan, Hubei, Peoples R ChinaHuazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Div Gastroenterol, Wuhan, Hubei, Peoples R China
机构:
Wannan Med Coll, Yijishan Hosp, Dept Gerontol, Wuhu 241001, Peoples R ChinaWannan Med Coll, Yijishan Hosp, Dept Gerontol, Wuhu 241001, Peoples R China
Wang, Deguo
Zhu, Hongjun
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Anhui Med Univ, Anhui Prov Hosp, Dept Cardiol, Hefei 230001, Peoples R ChinaWannan Med Coll, Yijishan Hosp, Dept Gerontol, Wuhu 241001, Peoples R China
Zhu, Hongjun
Yang, Qing
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Wannan Med Coll, Yijishan Hosp, Dept Gerontol, Wuhu 241001, Peoples R ChinaWannan Med Coll, Yijishan Hosp, Dept Gerontol, Wuhu 241001, Peoples R China
Yang, Qing
Sun, Yirun
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Wannan Med Coll, Yijishan Hosp, Dept Gerontol, Wuhu 241001, Peoples R ChinaWannan Med Coll, Yijishan Hosp, Dept Gerontol, Wuhu 241001, Peoples R China