Circulation. 2001;104:1670-1675
doi: 10.1161/hc4001.097186
doi: 10.1161/hc4001.097186
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(Circulation. 2001;104:1670.)
© 2001 American Heart Association, Inc.
Basic Science Reports |
Peroxisome Proliferator-Activated Receptor 
Activators Inhibit Cardiac Hypertrophy in Cardiac Myocytes
Department of Cardiology (K.Y., R.O., U.I., K.S.), Jichi Medical School, Minamikawachi-Machi, Tochigi, Japan, and the Cardiovascular Division (R.T.L.), Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass.
Correspondence to Keiji Yamamoto, MD, Department of Cardiology, Jichi Medical School, Minamikawachi-Machi, Tochigi, Japan 329-0498. E-mail kyamamoto{at}jichi.ac.jp
Background— Peroxisome proliferator-activated receptors (PPARs) are transcription factors belonging to the nuclear receptor superfamily. PPAR
mRNA is present in cardiac myocytes; however, whether PPAR affects cardiac hypertrophy remains unknown.
Methods and Results— We investigated the effects of PPAR activators on cardiac hypertrophy in neonatal rat cardiac myocytes. Cyclic 4% biaxial mechanical strain caused enlargement of cardiac myocytes (1.3-fold versus control, P<0.0001), but the PPAR activators troglitazone and 15-deoxy-
12-14-prostaglandin J2 (15d-PGJ2) (10 µmol/L) inhibited this effect (troglitazone, -72%, P<0.0005; 15d-PGJ2, -88%, P<0.0002). Total cell protein was increased by mechanical strain (control, 164.3 µg/dish; strain, 265.5, P<0.0002), and this effect was inhibited by troglitazone and 15d-PGJ2 (troglitazone, -61%, P<0.005; 15d-PGJ2, -72%, P<0.001). [3H]Leucine uptake was also increased by mechanical strain (1.9-fold versus control, P<0.002), and this increase was inhibited by troglitazone and 15d-PGJ2 (troglitazone, -52% at 10 µmol/L, P<0.01; 15d-PGJ2, -70% at 10 µmol/L, P<0.005). An increase in [3H]leucine uptake induced by angiotensin II or phenylephrine was significantly inhibited by troglitazone and 15d-PGJ2. Mechanical strain induced mRNA expression for brain natriuretic peptide, but PPAR activators inhibited this induction. Furthermore, PPAR activators inhibited mechanically induced activation of nuclear factor (NF)-
B. Pyrrolidine dithiocarbamate, an inhibitor of NF-B activation, inhibited strain-induced [3H]leucine uptake (-50% at 100 µmol/L, P<0.05).
Conclusions— These results demonstrate that PPAR activators inhibit cardiac hypertrophy in cardiac myocytes and suggest that PPAR activators may regulate cardiomyocyte hypertrophy at least partially through the NF-B pathway.
Key Words: hypertrophy • stress • myocytes
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