Peroxisome proliferator-activated receptor gamma activators inhibit cardiac hypertrophy in cardiac myocytes

Article; Proceedings Paper

关键词: SMOOTH-MUSCLE;    PPAR-GAMMA;    TISSUE DISTRIBUTION;    RAT-HEART;    GROWTH;    EXPRESSION;    TROGLITAZONE;    ALPHA;    CELLS;    REGULATOR;   

DOI  :  10.1161/hc4001.097186

来源: SCIE

【 摘 要 】

Background-Peroxisome proliferator-activated receptors (PPARs) are transcription factors belonging to the nuclear receptor superfamily. PPAR gamma mRNA is present in cardiac myocytes; however, whether PPAR gamma affects cardiac hypertrophy remains unknown. Methods and Results-We investigated the effects of PPAR gamma 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 gamma activators troglitazone and 15-deoxy-Delta (12-14)-prostaglandin J(2) (15d-PGJ(2)) (10 mu mol/L) inhibited this effect (troglitazone, -72%, P <0.0005; 15d-PGJ(2), -88%, P <0.0002). Total cell protein was increased by mechanical strain (control, 164.3 mug/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). [H-3]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-PGJ(2), (troglitazone, -52% at 10 mu moI/L, P <0.01; 15d-PGJ(2), -70% at 10 mu mol/L, P <0.005). An increase in [H-3]leucine uptake induced by angiotensin II or phenylephrine was significantly inhibited by troglitazone and 15d-PGJ(2). Mechanical strain induced mRNA expression for brain natriuretic peptide, but PPAR gamma activators inhibited this induction. Furthermore, PPAR gamma activators inhibited mechanically induced activation of nuclear factor (NF)-kappaB. Pyrrolidine dithiocarbamate, an inhibitor of NF-kappaB activation, inhibited strain-induced [H-3]leucine uptake (-50% at 100 mu mol/L, P <0.05). Conclusions These results demonstrate that PPAR gamma activators inhibit cardiac hypertrophy in cardiac myocytes and suggest that PPAR gamma activators may regulate cardiomyocyte hypertrophy at least partially through the NF-KB pathway.

【 授权许可】

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