PMID- 31070532
OWN - NLM
STAT- MEDLINE
DCOM- 20190904
LR  - 20200225
IS  - 1744-5116 (Electronic)
IS  - 1388-0209 (Print)
IS  - 1388-0209 (Linking)
VI  - 56
IP  - 1
DP  - 2018 Dec
TI  - Effect of simvastatin on the SIRT2/NF-kappaB pathway in rats with acute pulmonary 
      embolism.
PG  - 511-518
LID - 10.1080/13880209.2018.1508239 [doi]
AB  - CONTEXT: Statins have been widely used in acute pulmonary embolism (APE), while 
      simvastatin has been well-established for the prevention of pulmonary 
      hypertension, which was supposed to be an attractive recommendation for APE 
      treatment. OBJECTIVE: The current article studies the effect of simvastatin on 
      the SIRT2/NF-kappaB pathway in rats with APE. MATERIALS AND METHODS: Sprague-Dawley 
      rats were divided into four groups (n = 24 per group): control group, rats were 
      treated with saline once daily for 14 days before administration of saline (sham 
      group) or a suspension of autologous emboli (APE group), or rats were treated 
      with simvastatin (10 mg/kg) for 14 days before administration of autologous 
      emboli (APE + simvastatin) group. The RVSP, mPAP and the arterial blood gas was 
      analyzed. Besides, plasma inflammatory cytokines and MMPs levels, as well as the 
      expression of SIRT2/NF-kappaB pathway were determined. RESULTS: Compared with the 
      control and sham groups, the levels of mPAP (31.06 +/- 3.47 mmHg), RVSP 
      (35.12 +/- 6.02 mmHg), A-aDO(2) (33.14 +/- 6.16 mmHg) and MMP-9 (6.89 +/- 0.84 ng/mL) 
      activity were significantly elevated, but PaO(2) (66.87 +/- 7.85 mmHg) was highly 
      decreased in rats from APE group at 24 h after APE. Meanwhile, the inflammatory 
      changes were aggravated by the enhanced levels of TNF-alpha (138.85 +/- 22.69 pg/mL), 
      IL-1beta (128.47 +/- 22.14 pg/mL), IL-6 (103.16 +/- 13.58 pg/mL) and IL-8 
      (179.28 +/- 25.79 pg/mL), as well as increased NF-kappaB (5.29 +/- 0.47 fold), but 
      reduced SIRT2 (59 +/- 6% reduction), and eNOS (61 +/- 5% reduction) mRNA in APE rats. 
      APE rats treated with simvastatin led to a significant opposite trend of the 
      above indexes. CONCLUSIONS: Simvastatin protects against APE-induced pulmonary 
      artery pressure, hypoxemia and inflammatory changes probably due to the 
      regulation of SIRT2/NF-kappaB signalling pathway, which suggest that simvastatin may 
      have promising protective effects in patients with APE.
FAU - Wu, Zhi-Yao
AU  - Wu ZY
AD  - a Department of Respiratory Medicine (Department of Respiratory and Critical Care 
      Medicine), National Key Clinical Specialty, Xiangya Hospital , Central South 
      University , Changsha , China.
FAU - Li, Hui
AU  - Li H
AD  - a Department of Respiratory Medicine (Department of Respiratory and Critical Care 
      Medicine), National Key Clinical Specialty, Xiangya Hospital , Central South 
      University , Changsha , China.
FAU - Tang, Yong-Jun
AU  - Tang YJ
AD  - a Department of Respiratory Medicine (Department of Respiratory and Critical Care 
      Medicine), National Key Clinical Specialty, Xiangya Hospital , Central South 
      University , Changsha , China.
LA  - eng
PT  - Journal Article
PL  - England
TA  - Pharm Biol
JT  - Pharmaceutical biology
JID - 9812552
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (NF-kappa B)
RN  - 0 (Sirt2 protein, rat)
RN  - AGG2FN16EV (Simvastatin)
RN  - EC 3.5.1.- (Sirtuin 2)
SB  - IM
MH  - Animals
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology/*therapeutic use
MH  - Male
MH  - NF-kappa B/*antagonists & inhibitors/metabolism
MH  - Pulmonary Embolism/*drug therapy/metabolism/pathology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/drug effects/physiology
MH  - Simvastatin/pharmacology/*therapeutic use
MH  - Sirtuin 2/*antagonists & inhibitors/metabolism
MH  - Treatment Outcome
PMC - PMC6282435
OTO - NOTNLM
OT  - Inflammatory cytokines
OT  - MMPs
OT  - pulmonary artery pressure
EDAT- 2019/05/10 06:00
MHDA- 2019/09/05 06:00
PMCR- 2018/12/03
CRDT- 2019/05/10 06:00
PHST- 2019/05/10 06:00 [entrez]
PHST- 2019/05/10 06:00 [pubmed]
PHST- 2019/09/05 06:00 [medline]
PHST- 2018/12/03 00:00 [pmc-release]
AID - 1508239 [pii]
AID - 10.1080/13880209.2018.1508239 [doi]
PST - ppublish
SO  - Pharm Biol. 2018 Dec;56(1):511-518. doi: 10.1080/13880209.2018.1508239.