PMID- 31841211
OWN - NLM
STAT- MEDLINE
DCOM- 20201015
LR  - 20231020
IS  - 2284-0729 (Electronic)
IS  - 1128-3602 (Linking)
VI  - 23
IP  - 23
DP  - 2019 Dec
TI  - Effect of atorvastatin on pulmonary arterial hypertension in rats through 
      PI3K/AKT signaling pathway.
PG  - 10549-10556
LID - 19696 [pii]
LID - 10.26355/eurrev_201912_19696 [doi]
AB  - OBJECTIVE: The aim of this study was to investigate the effect of atorvastatin on 
      pulmonary arterial hypertension (PAH) in rats and to observe its specific 
      regulatory mechanism through the phosphatidylinositol 3-hydroxy kinase/protein 
      kinase B (PI3K/AKT) signaling pathway. MATERIALS AND METHODS: The model of PAH 
      was successfully established in rats via hypoxia feeding. All rats were divided 
      into three groups, including Control group (n=15), PAH model group (Model group, 
      n=15) and atorvastatin treatment group (Ator group, n=15). Tumor necrosis 
      factor-alpha (TNF-alpha), interleukin-6 (IL-6) and nitric oxide (NO) were detected via 
      enzyme-linked immunosorbent assay (ELISA). Right ventricular systolic pressure 
      (RVSP) and right ventricular hypertrophy index (RVHI) in each group were 
      determined as well. Meanwhile, the pathological changes in lung tissues of rats 
      were detected via hematoxylin-eosin (HE) staining. Furthermore, the apoptosis 
      level of lung tissues in each group was detected via terminal deoxynucleotidyl 
      transferase-mediated dUTP nick-end labeling (TUNEL) staining. In addition, the 
      expression levels of PI3K/AKT signaling pathway and apoptotic genes in lung 
      tissues were detected via quantitative Polymerase Chain Reaction (qPCR). RESULTS: 
      In Model group, the levels of TNF-alpha and IL-6 increased significantly, while the 
      level of NO decreased. Both RVSP and RVHI in Model group were significantly 
      higher than those of Control group and Ator group (p<0.05). The results of HE 
      staining revealed that Model group showed significantly severe lung tissue injury 
      (p<0.05). According to the results of TUNEL staining, the number of apoptotic 
      cells in lung tissues in Model group was significantly smaller than that of Ator 
      group (p<0.05). Meanwhile, the expression level of cysteinyl aspartate-specific 
      proteinase-3 (Caspase-3) in Model group was markedly lower than that of Ator 
      group (p<0.05). However, the expression level of B-cell lymphoma-2 (Bcl-2) in 
      Model group was markedly higher than that of Ator group (p<0.05). In Ator group, 
      the expression levels of PI3K and AKT in lung tissues were remarkably higher than 
      those of Model group (p<0.05). All the above results indicated that atorvastatin 
      could effectively up-regulate the expressions of PI3K and AKT (p<0.05). 
      CONCLUSIONS: Atorvastatin regulates the symptoms of PAH in rats through 
      activating the PI3K/AKT signaling pathway.
FAU - Wang, Y-Y
AU  - Wang YY
AD  - Neonatal Intensive Care Unit, Affiliated Hospital of Jining Medical College, 
      Jining, China. 7100668@163.com.
FAU - Cheng, X-D
AU  - Cheng XD
FAU - Jiang, H
AU  - Jiang H
LA  - eng
PT  - Journal Article
PT  - Retracted Publication
PL  - Italy
TA  - Eur Rev Med Pharmacol Sci
JT  - European review for medical and pharmacological sciences
JID - 9717360
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - A0JWA85V8F (Atorvastatin)
RN  - EC 2.7.11.1 (Akt1 protein, rat)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
RIN - Eur Rev Med Pharmacol Sci. 2023 Sep;27(17):7881. PMID: 37750615
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Atorvastatin/*pharmacology/therapeutic use
MH  - Disease Models, Animal
MH  - Humans
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacology/therapeutic use
MH  - Male
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Pulmonary Arterial Hypertension/*drug therapy/pathology
MH  - Pulmonary Artery/*drug effects/pathology
MH  - Rats
MH  - Signal Transduction/*drug effects
MH  - Up-Regulation/drug effects
EDAT- 2019/12/17 06:00
MHDA- 2020/10/21 06:00
CRDT- 2019/12/17 06:00
PHST- 2019/12/17 06:00 [entrez]
PHST- 2019/12/17 06:00 [pubmed]
PHST- 2020/10/21 06:00 [medline]
AID - 19696 [pii]
AID - 10.26355/eurrev_201912_19696 [doi]
PST - ppublish
SO  - Eur Rev Med Pharmacol Sci. 2019 Dec;23(23):10549-10556. doi: 
      10.26355/eurrev_201912_19696.