Abstract:
:Aspirin (ASA) is a cardioprotective drug with anti-cardiac fibrosis action in vivo. This study was aimed to clarify the anti-cardiac fibrosis action of ASA and the underlying mechanisms. Two heart injury models (injection of isoproterenol and ligation of the left anterior descending branch) were used in mice to induce cardiac fibrosis. The animals were treated with ASA (10 mg·kg-1·d-1, ig) for 21 and 14 d, respectively. ASA administration significantly improved cardiac function, and ameliorated heart damage and fibrosis in the mice. The mechanisms underlying ASA's anti-fibrotic effect were further analyzed in neonatal cardiac fibroblasts (CFs) exposed to hypoxia in vitro. ASA (0.5-5 mmol/L) dose-dependently inhibited the proliferation and Akt phosphorylation in the CFs. In addition, ASA significantly inhibited CF apoptosis, and decreased the levels of apoptosis markers (cleaved caspase 3 and Parp1), which might serve as a side effect of anti-fibrotic effect of ASA. Furthermore, ASA dose-dependently inhibited the autophagy in the CFs, as evidenced by the reduced levels of autophagy marker LC3-II. The autophagy inhibitor Pepstatin A (PepA) promoted the inhibitory effect of ASA on CF proliferation, whereas the autophagy inducer rapamycin rescued ASA-caused inhibition of CF proliferation, suggesting an autophagy-dependent anti-proliferative effect of ASA. Both p38 inhibitor SB203580 and ROS scavenger N-acetyl-cysteine (NAC) significantly decreased Akt phosphorylation in CFs in the basal and hypoxic situations, but they both significantly increased LC3-II levels in the CFs. Our results suggest that an autophagy- and p38/ROS-dependent pathway mediates the anti-cardiac fibrosis effect of ASA in CFs. As PepA and SB203580 did not affect ASA-caused inhibition of CF apoptosis, the drug combination will enhance ASA's therapeutic effects.
journal_name
Acta Pharmacol Sinjournal_title
Acta pharmacologica Sinicaauthors
Liu PP,Liu HH,Sun SH,Shi XX,Yang WC,Su GH,Zhao Jdoi
10.1038/aps.2016.143subject
Has Abstractpub_date
2017-04-01 00:00:00pages
488-497issue
4eissn
1671-4083issn
1745-7254pii
aps2016143journal_volume
38pub_type
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abstract:AIM:Extract of Hominis Placenta (HP) has been used in oriental medicine as an agent for improving physiological function. The present study was conducted to investigate whether HP treatment in an experimental sciatic nerve injury animal model produces growth-promoting effects on regenerating peripheral nerve fibers aft...
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
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更新日期:2012-10-01 00:00:00
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pub_type: 杂志文章
doi:10.1038/s41401-020-0409-3
更新日期:2020-12-01 00:00:00
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pub_type: 杂志文章
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更新日期:2020-03-01 00:00:00
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journal_title:Acta pharmacologica Sinica
pub_type: 临床试验,杂志文章
doi:
更新日期:2001-05-01 00:00:00
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pub_type: 杂志文章
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更新日期:2017-07-01 00:00:00
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pub_type: 杂志文章
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更新日期:2018-07-01 00:00:00
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pub_type: 杂志文章,评审
doi:10.1111/j.1745-7254.2006.00401.x
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
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更新日期:2005-09-01 00:00:00
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pub_type: 杂志文章
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更新日期:2012-12-01 00:00:00
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更新日期:2019-05-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2015-01-01 00:00:00
abstract::AIDS is presently treatable, and patients can have a good prognosis due to the success of highly active antiretroviral therapy (HAART), but it is still not curable or preventable. High toxicity of HAART, and the emergence of drug resistance add to the imperative to continue research into new strategies and interventio...
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pub_type: 杂志文章,评审
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更新日期:2005-10-01 00:00:00
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
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更新日期:2000-11-01 00:00:00
abstract:AIM:To determine propofol concentration in the cerebral spinal fluid (CSF) of neurosurgical patients and carry out a preliminary population pharmacodynamic study. METHODS:Twenty-seven elective neurosurgical patients (12 men and 15 women) aged 17-74 years received propofol in a bolus dose of 2 mg/kg for 5 min and an in...
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pub_type: 杂志文章
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更新日期:2006-05-01 00:00:00
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更新日期:2021-01-25 00:00:00