Lai J, Jin H, Yang R, Winer J, Li W, Yen R, King K L, Zeigler F, Ko A, Cheng J, Bunting S, Paoni N F
Department of Cardiovascular Research, Genentech, Inc., South San Francisco, California 94080, USA.
Am J Physiol. 1996 Dec;271(6 Pt 2):H2197-208. doi: 10.1152/ajpheart.1996.271.6.H2197.
Several prostaglandins [prostaglandin (PG) A2, -B2, -D2, -E2, -F2 alpha, and -I2 and carbaprostacyclin] and the thromboxane analogue U-46619 were analyzed for the ability to induce hypertrophy of rat neonatal cardiac ventricular myocytes. Myocyte hypertrophy was induced specifically by PGF2 alpha. Myocytes exposed to this prostanoid in culture increased in size and protein content. The contractile fibrils within the cells became organized into parallel arrays, and the cells tended to cluster and beat spontaneously. PGF2 alpha also induced the expression of c-fos, atrial natriuretic factor (ANF), and alpha-skeletal actin in these cells. The effects of PGF2 alpha were compared with several known cardiac myocyte hypertrophy factors (phenylephrine, endothelin-1, leukemia inhibitory factor, cardiotrophin-1, and angiotensin II). PGF2 alpha was found to be intermediate in potency among the factors but induced a level of ANF production that was approximately 10-fold higher than any of the other effectors. Responsiveness to PGF2 alpha was not limited to neonatal cardiocytes. Ventricular myocytes isolated from adult rats also responded specifically to PGF2 alpha with a morphological change similar to that observed with phenylephrine and by producing ANF. In rats, chronic administration of fluprostenol, a potent agonist analogue of PGF2 alpha, resulted in a dose-dependent increase in heart weight- and ventricular weight-to-body weight ratios. The amount of PGF2 alpha extractable from the hearts of rats with cardiac hypertrophy induced by myocardial infarction was also found to be greater than that in sham-operated control rats. These results indicate that PGF2 alpha may play an important role in inducing cardiac hypertrophy.
对几种前列腺素（前列腺素（PG）A2、-B2、-D2、-E2、-F2α和-I2以及卡前列环素）和血栓素类似物U-46619诱导大鼠新生心室心肌细胞肥大的能力进行了分析。PGF2α特异性诱导心肌细胞肥大。培养中暴露于这种前列腺素的心肌细胞大小和蛋白质含量增加。细胞内的收缩性纤维束排列成平行阵列，细胞倾向于聚集并自发搏动。PGF2α还诱导这些细胞中c-fos、心房利钠因子（ANF）和α-骨骼肌动蛋白的表达。将PGF2α的作用与几种已知的心肌细胞肥大因子（去氧肾上腺素、内皮素-1、白血病抑制因子、心肌营养素-1和血管紧张素II）进行了比较。发现PGF2α在这些因子中的效力处于中等水平，但诱导的ANF产生水平比任何其他效应物高约10倍。对PGF2α的反应性不限于新生心肌细胞。从成年大鼠分离的心室肌细胞也对PGF2α有特异性反应，其形态变化类似于去氧肾上腺素引起的变化，并产生ANF。在大鼠中，长期给予氟前列烯醇（一种PGF2α的强效激动剂类似物）导致心脏重量以及心室重量与体重之比呈剂量依赖性增加。还发现，心肌梗死诱导的心脏肥大大鼠心脏中可提取的PGF2α量大于假手术对照大鼠。这些结果表明，PGF2α可能在诱导心脏肥大中起重要作用。
