TY - JOUR
T1 - Regulation of the cardiomyocyte population in the developing heart
AU - Thornburg, Kent
AU - Jonker, Sonnet
AU - O'Tierney, Perrie
AU - Chattergoon, Natasha
AU - Louey, Samantha
AU - Faber, Job
AU - Giraud, George
N1 - Funding Information:
This study was supported by funds from NICHD P01 HD 34430 , NHLBI R21 HL093617 , and R01 HL102763 . Dr. Natasha Chattergoon was supported by NHLBI training grant T32HL094294 . Dr. Sonnet Jonker was supported by Office of Research on Women’s Health and the National Institute of Child Health and Human Development, Oregon BIRCWH HD043488. Dr. Thornburg was supported by the M. Lowell Edwards Endowment.
PY - 2011/7
Y1 - 2011/7
N2 - During fetal life the myocardium expands through replication of cardiomyocytes. In sheep, cardiomyocytes begin the process of becoming terminally differentiated at about 100 gestation days out of 145 days term. In this final step of development, cardiomyocytes become binucleated and stop dividing. The number of cells at birth is important in determining the number of cardiomyocytes for life. Therefore, the regulation of cardiomyocyte growth in the womb is critical to long term disease outcome. Growth factors that stimulate proliferation of fetal cardiomyocytes include angiotensin II, cortisol and insulin-like growth factor-1. Increased ventricular wall stress leads to short term increases in proliferation but longer-term loss of cardiomyocyte generative capacity. Two normally circulating hormones have been identified that suppress proliferation: atrial natriuretic peptide (ANP) and tri-iodo-l-thyronine (T3). Atrial natriuretic peptide signals through the NPRA receptor that serves as a guanylate cyclase and signals through cGMP. ANP powerfully suppresses mitotic activity in cardiomyocytes in the presence of angiotensin II in culture. Addition of a cGMP analog has the same effect as ANP. ANP suppresses both the extracellular receptor kinases and the phosphoinositol-3 kinase pathways. T3 also suppresses increased mitotic activity of stimulated cardiomyocytes but does so by increasing the cell cycle suppressant, p21, and decreasing the cell cycle activator, cyclin D1.
AB - During fetal life the myocardium expands through replication of cardiomyocytes. In sheep, cardiomyocytes begin the process of becoming terminally differentiated at about 100 gestation days out of 145 days term. In this final step of development, cardiomyocytes become binucleated and stop dividing. The number of cells at birth is important in determining the number of cardiomyocytes for life. Therefore, the regulation of cardiomyocyte growth in the womb is critical to long term disease outcome. Growth factors that stimulate proliferation of fetal cardiomyocytes include angiotensin II, cortisol and insulin-like growth factor-1. Increased ventricular wall stress leads to short term increases in proliferation but longer-term loss of cardiomyocyte generative capacity. Two normally circulating hormones have been identified that suppress proliferation: atrial natriuretic peptide (ANP) and tri-iodo-l-thyronine (T3). Atrial natriuretic peptide signals through the NPRA receptor that serves as a guanylate cyclase and signals through cGMP. ANP powerfully suppresses mitotic activity in cardiomyocytes in the presence of angiotensin II in culture. Addition of a cGMP analog has the same effect as ANP. ANP suppresses both the extracellular receptor kinases and the phosphoinositol-3 kinase pathways. T3 also suppresses increased mitotic activity of stimulated cardiomyocytes but does so by increasing the cell cycle suppressant, p21, and decreasing the cell cycle activator, cyclin D1.
KW - Atrial natriuretic peptide
KW - Cardiomyocyte
KW - Fetus
KW - Programming
KW - Terminal differentiation
KW - Tri-iodo-l-thyronine
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U2 - 10.1016/j.pbiomolbio.2010.11.010
DO - 10.1016/j.pbiomolbio.2010.11.010
M3 - Review article
C2 - 21147149
AN - SCOPUS:79957972533
SN - 0079-6107
VL - 106
SP - 289
EP - 299
JO - Progress in Biophysics and Molecular Biology
JF - Progress in Biophysics and Molecular Biology
IS - 1
ER -