| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Received January 2, 2003
Accepted after revision January 30, 2003
1 Department of Physiology/Pharmacology, Oregon Health and Science University, Portland, OR, USA
2 Departments of Physiology/Pharmacology and Medicine (Cardiology), Portland VA Medical Center and Heart Research Center, Oregon Health and Science University, Portland, OR, USA
3 The Vollum Institute for Advanced Biomedical Research and Heart Research Center, Oregon Health and Science University, Portland, OR, USA
4 Departments of Obstetrics and Gynecology and Heart Research Center, Oregon Health and Science University, Portland, OR, USA
5 Heart Research Center, L464, School of Medicine, Oregon Health and Science University, Portland, OR 97239, USA
* To whom correspondence should be addressed. E-mail: thornbur{at}ohsu.edu.
Rat and sheep cardiac myocytes become binucleate as they complete the 'terminal differentiation' process soon after birth and are not able to divide thereafter. Angiotensin II (Ang II) is known to stimulate hypertrophic changes in rodent cardiomyocytes under both in vivo and in vitro conditions via the AT1 receptor and intracellular ERK signalling cascade. We sought to develop culture methods for immature sheep cardiomyocytes in order to test the hypothesis that Ang II is a hypertrophic agent in the immature myocardium of the sheep. We isolated fetal sheep cardiomyocytes and cultured them for 96 h, added Ang II and phenylephrine (PE) for 48 h, and measured footprint area and proliferation (5-bromo-2â-deoxyuridine (BrdU) uptake) separately in mono- vs. binucleate myocytes. We found that neither Ang II nor PE changed the footprint area of mononucleated cells. PE stimulated an increase in footprint area of binucleate cells but Ang II did not. Ang II increased myocyte BrdU uptake compared to serum free conditions, but PE did not affect BrdU uptake. The MEK inhibitor UO126 prevented BrdU uptake in Ang II-stimulated cells and prevented cell hypertrophy in PE-stimulated cells. This paper establishes culture methods for immature sheep cardiomyocytes and reports that: (1) Ang II is not a hypertrophic agent; (2) Ang II stimulates hyperplastic growth among mononucleate myocytes; (3) PE is a hypertrophic agent in binucleate myocytes; and (4) the ERK cascade is required for the proliferation effect of Ang II and the hypertrophic effect of PE.
This article has been cited by other articles:
|
|
 |
|
  J. L. Morrison, K. J. Botting, J. L. Dyer, S. J. Williams, K. L. Thornburg, and I. C. McMillen Restriction of placental function alters heart development in the sheep fetus Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2007; 293(1): R306 - R313. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Louey, S. S. Jonker, G. D. Giraud, and K. L. Thornburg Placental insufficiency decreases cell cycle activity and terminal maturation in fetal sheep cardiomyocytes J. Physiol., April 15, 2007; 580(2): 639 - 648. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. S. Jonker, L. Zhang, S. Louey, G. D. Giraud, K. L. Thornburg, and J. J. Faber Myocyte enlargement, differentiation, and proliferation kinetics in the fetal sheep heart J Appl Physiol, March 1, 2007; 102(3): 1130 - 1142. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N N Chattergoon, G D Giraud, and K L Thornburg Thyroid hormone inhibits proliferation of fetal cardiac myocytes in vitro J. Endocrinol., February 1, 2007; 192(2): R1 - R8. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S. Jonker, J. J. Faber, D. F. Anderson, K. L. Thornburg, S. Louey, and G. D. Giraud Sequential growth of fetal sheep cardiac myocytes in response to simultaneous arterial and venous hypertension Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2007; 292(2): R913 - R919. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Reini, C. E. Wood, E. Jensen, and M. Keller-Wood Increased maternal cortisol in late-gestation ewes decreases fetal cardiac expression of 11beta-HSD2 mRNA and the ratio of AT1 to AT2 receptor mRNA Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2006; 291(6): R1708 - R1716. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. N. Spencer, K. J. Botting, J. L. Morrison, and G. S. Posterino Contractile and Ca2+-handling properties of the right ventricular papillary muscle in the late-gestation sheep fetus J Appl Physiol, September 1, 2006; 101(3): 728 - 733. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. D. Giraud, S. Louey, S. Jonker, J. Schultz, and K. L. Thornburg Cortisol Stimulates Cell Cycle Activity in the Cardiomyocyte of the Sheep Fetus Endocrinology, August 1, 2006; 147(8): 3643 - 3649. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. K. Olson, K. N. Protheroe, T. D. Scholz, and J. L. Segar The Mitogen-Activated Protein Kinases and Akt Are Developmentally Regulated in the Chronically Anemic Fetal Sheep Heart Reproductive Sciences, April 1, 2006; 13(3): 157 - 165. [Abstract] [PDF]
|
|
|
|
 |
|
 A. K. Olson, K. N. Protheroe, J. L. Segar, and T. D. Scholz Mitogen-activated protein kinase activation and regulation in the pressure-loaded fetal ovine heart Am J Physiol Heart Circ Physiol, April 1, 2006; 290(4): H1587 - H1595. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. C. Mcmillen and J. S. Robinson Developmental Origins of the Metabolic Syndrome: Prediction, Plasticity, and Programming Physiol Rev, April 1, 2005; 85(2): 571 - 633. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. R. Lumbers, A. C. Boyce, G. Joulianos, V. Kumarasamy, E. Barner, J. L. Segar, and J. H. Burrell Effects of cortisol on cardiac myocytes and on expression of cardiac genes in fetal sheep Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2005; 288(3): R567 - R574. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Otis, S. Campbell, M. D. Payet, and N. Gallo-Payet Angiotensin II Stimulates Protein Synthesis and Inhibits Proliferation in Primary Cultures of Rat Adrenal Glomerulosa Cells Endocrinology, February 1, 2005; 146(2): 633 - 642. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Schreckenberg, G. Taimor, H. M. Piper, and K.-D. Schluter Inhibition of Ca2+-dependent PKC isoforms unmasks ERK-dependent hypertrophic growth evoked by phenylephrine in adult ventricular cardiomyocytes Cardiovasc Res, August 15, 2004; 63(3): 553 - 560. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A L Fowden and A J Forhead Endocrine mechanisms of intrauterine programming Reproduction, May 1, 2004; 127(5): 515 - 526. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Forhead and A. L. Fowden Role of angiotensin II in the pressor response to cortisol in fetal sheep during late gestation Exp Physiol, May 1, 2004; 89(3): 323 - 329. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. C. Sundgren, G. D. Giraud, J. M. Schultz, M. R. Lasarev, P. J. S. Stork, and K. L. Thornburg Extracellular signal-regulated kinase and phosphoinositol-3 kinase mediate IGF-1 induced proliferation of fetal sheep cardiomyocytes Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2003; 285(6): R1481 - R1489. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
