[Simvastatin attenuated cardiac hypertrophy via inhibiting JAK-STAT pathways].
OBJECTIVE
To investigate the effects of simvastatin (SIM) on in vivo and in vitro cardiac hypertrophy models and changes on JAK/STAT signal pathways.


METHODS
Myocardial hypertrophy was induced by Cardiotrophin-1 (CT-1) in neonatal cardiomyocytes and by abdominal aortic constriction (AC) for 4 weeks in adult SD rats. In vitro study groups were as follows (n = 3 each): (1) control, (2) CT-1 (10(-10) mol/L), (3) CT-1 + SIM (10(-6) mol/L), (4) CT-1 + AG490(JAK inhibitor, 10(-4) mol/L), (5)SIM (10(-6) mol/L), (6) AG490 (10(-4) mol/L). In vivo study groups were as follows (n = 8 each): (1) sham group, (2) AC group, (3) AC + SIM group, (4) AC + captopril group. Total protein content was measured by Lowry's method and the cell surface area was measured by phase contrast microscope. The expression of AGT mRNA and c-fos mRNA were detected by RT-PCR. Systolic blood pressure (SBP), heart weight/body weight (HW/BW) and left ventricle weight/body weight (LVW/BW) were measured. The expressions of p-JAK2 and p-STAT3 were detected by Western blot.


RESULTS
The total protein content and cardiomyocytes size were significantly increased in CT-1 treated cells and which could be blocked by SIM. The expressions of p-JAK2 and p-STAT3 as well as the expression of AGT mRNA and c-fos mRNA significantly activated by CT-1, which could be inhibited by SIM or Janus Kinase-selective inhibitor AG490. Similar as captopril, SIM also attenuated cardiac hypertrophy in AC rats as shown on reduced systolic blood pressure, heart weight to body weight, left ventricular weight to body weight ratios as well as cross sectional area of cardiomyocytes.


CONCLUSIONS
SIM prevented CT-1 and AC induced cardiomyocyte hypertrophy via inhibiting JAK/STAT pathways.
Wu
Yang
Y
Institute of Navigation Medicine, Nantong University, Nantong 226001, China.
Liu
Juan
J
D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism* / Q000517:prevention & control*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000378:metabolism; D053612:Janus Kinases / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D019821:Simvastatin / Q000494:pharmacology*
D016207:Cytokines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D050791:STAT Transcription Factors; D019821:Simvastatin; C092073:cardiotrophin 1; D053612:Janus Kinases