PMID- 31957855
OWN - NLM
STAT- MEDLINE
DCOM- 20210101
LR  - 20210101
IS  - 2284-0729 (Electronic)
IS  - 1128-3602 (Linking)
VI  - 24
IP  - 1
DP  - 2020 Jan
TI  - Losartan promotes myocardial apoptosis after acute myocardial infarction in rats 
      through inhibiting Ang II-induced JAK/STAT pathway.
PG  - 409-417
LID - 19939 [pii]
LID - 10.26355/eurrev_202001_19939 [doi]
AB  - OBJECTIVE: To study the pro-apoptotic effect of Losartan on myocardial cells 
      after acute myocardial infarction (AMI) in rats. MATERIALS AND METHODS: Before 
      intervention, a total of 48 male Wistar rats were randomly divided into the Sham 
      group (n=12), AMI group (n=12), 5 mg/kg Losartan group (n=12) and 1 mg/kg AG-490 
      group (n=12). The rats in the Sham group and AMI group received gavage with 
      normal saline, those in the Losartan group received gavage with Losartan for 7 d 
      and those in the AG-490 group were intravenously injected with AG-490 at 30 min 
      before the operation. At 4 d after drug administration, the anterior descending 
      coronary artery was ligated to establish the AMI model in the AMI group and 
      Losartan group, while the same operation was performed, and the anterior 
      descending coronary artery was only threaded in the Sham group. The rats were 
      sacrificed at 24 h after operation. Then, the myocardial apoptosis was detected 
      via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) 
      assay, and the protein expressions of Janus kinase 2 (JAK2), the signal 
      transducer and activator of transcription 3 (STAT3), the B-cell lymphoma-2 
      (Bcl-2) and the Bcl-2 associated X protein (Bax) were detected via 
      immunohistochemistry and Western blotting. Moreover, the myocardial cells of rats 
      were incubated with angiotensin II (Ang II) at the same concentration at 
      different time points and blocked with Losartan. Finally, the changes in protein 
      expressions of p-JAK2, p-STAT3, Bax, and Bcl-2 were detected via Western 
      blotting. RESULTS: Losartan treatment could increase the number of apoptotic 
      myocardial cells after AMI in rats. In Losartan group, the protein expressions of 
      JAK2, STAT3, and Bcl-2 declined, while the protein expression of Bax was 
      increased, and the Bax/Bcl-2 ratio was also increased, which are consistent with 
      the conditions under the treatment with the JAK-STAT pathway inhibitor AG-490. 
      With the prolonged time of stimulation (5 min, 30 min, 2 h, and 24 h) in 
      myocardial cells using 1.0x10-6 mol/L Ang II, the protein expressions of p-JAK2 
      and p-STAT3 were increased and reached the peak at 24 h. After the application of 
      Losartan, the increased protein expressions of p-JAK2 and p-STAT3 returned to 
      normal levels, and the protein expression of Bax was increased, while that of 
      Bcl-2 was decreased. CONCLUSIONS: Losartan promotes myocardial apoptosis after 
      AMI in the rats through inhibiting the Ang II-induced JAK/STAT pathway.
FAU - Xin, L-H
AU  - Xin LH
AD  - Department of Cardiology, People's Hospital of Lanling County, Linyi, China. 
      doctorsyang@163.com.
FAU - Liu, R
AU  - Liu R
FAU - Yang, X-W
AU  - Yang XW
LA  - eng
PT  - Journal Article
PL  - Italy
TA  - Eur Rev Med Pharmacol Sci
JT  - European review for medical and pharmacological sciences
JID - 9717360
RN  - 0 (Antihypertensive Agents)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Stat3 protein, rat)
RN  - 11128-99-7 (Angiotensin II)
RN  - EC 2.7.10.2 (Jak2 protein, rat)
RN  - EC 2.7.10.2 (Janus Kinase 2)
RN  - JMS50MPO89 (Losartan)
SB  - IM
MH  - Acute Disease
MH  - Angiotensin II/pharmacology
MH  - Animals
MH  - Antihypertensive Agents/administration & dosage/*pharmacology
MH  - Apoptosis/drug effects
MH  - Disease Models, Animal
MH  - Injections, Intraperitoneal
MH  - Janus Kinase 2/*antagonists & inhibitors/metabolism
MH  - Losartan/administration & dosage/*pharmacology
MH  - Male
MH  - Myocardial Infarction/*drug therapy/metabolism/pathology
MH  - Myocytes, Cardiac/*drug effects/metabolism/pathology
MH  - Rats
MH  - Rats, Wistar
MH  - STAT3 Transcription Factor/*antagonists & inhibitors/metabolism
EDAT- 2020/01/21 06:00
MHDA- 2021/01/02 06:00
CRDT- 2020/01/21 06:00
PHST- 2020/01/21 06:00 [entrez]
PHST- 2020/01/21 06:00 [pubmed]
PHST- 2021/01/02 06:00 [medline]
AID - 19939 [pii]
AID - 10.26355/eurrev_202001_19939 [doi]
PST - ppublish
SO  - Eur Rev Med Pharmacol Sci. 2020 Jan;24(1):409-417. doi: 
      10.26355/eurrev_202001_19939.