Systemic arterial hypertension but not IGF-I treatment stimulates cardiomyocyte enlargement in neonatal lambs
| Autor: | Samantha Louey, Terry K. Morgan, Nainesh Gandhi, Sonnet S. Jonker, Adrienne Wilburn, George D. Giraud |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Physiology Heart Ventricles 030204 cardiovascular system & hematology Muscle hypertrophy 03 medical and health sciences Fetus 0302 clinical medicine Physiology (medical) Internal medicine medicine Animals Humans Myocyte Myocytes Cardiac Insulin-Like Growth Factor I Sheep Systemic arterial hypertension business.industry Myocardium Cardiac myocyte Infant Newborn Hypertrophy Hyperplasia medicine.disease Recombinant Proteins 030104 developmental biology Endocrinology Hypertension business Research Article |
| Zdroj: | American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 315:R1038-R1048 |
| ISSN: | 1522-1490 0363-6119 |
| DOI: | 10.1152/ajpregu.00198.2018 |
| Popis: | Although cardiomyocyte terminal differentiation is nearly complete at birth in sheep, as in humans, very limited postnatal expansion of myocyte number may occur. The capacity of newborn cardiomyocytes to respond to growth stimulation by proliferation is poorly understood. Our objective was to test this growth response in newborn lambs with two stimuli shown to be potent inducers of cardiomyocyte growth in fetuses and adults: increased systolic load (Load) and insulin-like growth factor I (IGF-I). Vascular catheters and an inflatable aortic occluder were implanted in lambs. Hearts were collected for analysis at 18 days of age after a 7-day experiment and compared with control hearts. Load hearts, but not IGF-I hearts, were heavier ( P = 0.001) because of increased mass of the left ventricle (LV), septum, and left atrium (40–50%, P = 0.004). Terminal differentiation and cell cycle activity were not different between groups. Myocyte length was 7% greater in Load lamb hearts ( P < 0.05), and binucleated myocytes, which comprise ~90% of LV cells, were 25% larger in volume ( P = 0.03). Myocyte number per gram of myocardium was decreased in all ventricles of Load lambs ( P = 0.01). Cells from the IGF-I group were not different by any comparison. These results suggest that the newborn sheep LV responds to systolic stress with cardiomyocyte hypertrophy, not proliferation. Furthermore, IGF-I is ineffective at stimulating cardiomyocyte proliferation at this age (despite effectiveness when administered before birth). Thus, to expand cardiomyocyte number in the newborn heart, therapies other than systolic pressure load and IGF-I treatment need to be developed. |
| Databáze: | OpenAIRE |
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