Prostaglandin f2[alpha] induces cardiac myocyte hypertrophy in
vitro and cardiac growth in vivo.
Lai, Jadine, Hongkui Jin, Renhui Yang, Jane Winer, Wei Li, Randy Yen,
Kathleen L. King, Francis Zeigler, Annie Ko, Jennifer Cheng, Stuart
Bunting, and Nicholas F. Paoni.
Departments of Cardiovascular Research, BioAnalytical Technology,
and the Cell Biology Group, Genentech, Inc., 460 Point San Bruno
Blvd., South San Francisco, CA 94080
APStracts 3:0310H, 1996.
Several prostaglandins (A2, B2, D2, E2, F2[alpha], I2 and
carbaprostacyclin) and the thromboxane analogue U46619 were analyzed
for the ability to induce hypertrophy of rat neonatal cardiac
ventricular myocytes. Myocyte hypertrophy was induced specifically by
prostaglandin F2[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. F2[alpha] also
induced the expression of c-fos, ANF, and [alpha]-skeletal actin in
these cells. The effects of F2[alpha] were compared to several known
cardiac myocyte hypertrophy factors (phenylephrine, endothelin-1,
leukemia inhibitory factor (LIF), cardiotrophin-1 (CT-1), and
angiotensin II). F2[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 F2[alpha] was not limited to neonatal cardiocytes.
Ventricular myocytes isolated from adult rats also responded
specifically to F2[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
prostaglandin F2[alpha], resulted in a dose dependent increase in
heart weight and ventricular weight to body weight ratios. The amount
of F2[alpha] extractable from the hearts of rats with cardiac
hypertrophy induced by myocardial infarction was also found to be
greater than that of sham operated controls. These results indicate
that F2[alpha] may play an important role in inducing cardiac
hypertrophy.
Received 20 October 1995; accepted in final form 29 April 1996.
APS Manuscript Number H978-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 July 1996