Cardiomyocyte cell cycling, maturation, and growth by multinucleation in postnatal swine
| Autor: | Emma J Agnew, Kyle W. Riggs, Sithara Raju Ponny, Katherine E. Yutzey, Christina M. Alfieri, R. Scott Baker, Farhan Zafar, Nivedhitha Velayutham |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cell cycle checkpoint Swine Heart growth Cell Carboxylic Acids 030204 cardiovascular system & hematology Cell junction Muscle hypertrophy Extracellular matrix 0302 clinical medicine Gene expression Myocytes Cardiac Neurons education.field_of_study 0303 health sciences Cell Cycle Gap Junctions Extracellular Matrix Up-Regulation medicine.anatomical_structure 030220 oncology & carcinogenesis Cardiology and Cardiovascular Medicine Signal Transduction Sarcomeres Heart Ventricles Population Down-Regulation Mitosis Biology Models Biological Article Andrology 03 medical and health sciences medicine Animals Weaning education Molecular Biology Cell Proliferation 030304 developmental biology Cell Nucleus Fetus Regeneration (biology) Hypertrophy Diploidy 030104 developmental biology Animals Newborn Reactive Oxygen Species Transcriptome |
| Zdroj: | J Mol Cell Cardiol |
| Popis: | AimsCardiomyocyte (CM) cell cycle arrest, decline of mononucleated-diploid CMs, sarcomeric maturation, and extracellular matrix remodeling are implicated in loss of cardiac regenerative potential in mice after birth. Recent studies show a 3-day neonatal regenerative capacity in pig hearts similar to mice, but postnatal pig CM growth dynamics are unknown. We examined cardiac maturation in postnatal pigs and mice, to determine the relative timing of developmental events underlying heart growth and regenerative potential in large and small mammals.Methods and ResultsLeft ventricular tissue from White Yorkshire-Landrace pigs at postnatal day (P)0 to 6 months (6mo) was analyzed to span birth, weaning, and adolescence in pigs, compared to similar physiological timepoints in mice. Collagen remodeling increases by P7 in postnatal pigs, but sarcomeric and gap junctional maturation only occur at 2mo. Also, there is no postnatal transition to beta-oxidation metabolism in pig hearts. Mononucleated CMs, predominant at birth, persist to 2mo in swine, with over 50% incidence of mononucleated-diploid CMs at P7-P15. Extensive multinucleation with 4-16 nuclei per CM occurs beyond P30. Pigs also exhibit increased CM length relative to multinucleation, preceding increase in CM width at 2mo-6mo. Further, robust CM mitotic nuclear pHH3 activity and cardiac cell cycle gene expression is apparent in pig left ventricles up to 2mo. By contrast, in mice, these maturational events occur concurrently in the first two postnatal weeks alongside loss of cardiac regenerative capacity.ConclusionsCardiac maturation occurs over a 6mo postnatal period in pigs, despite a similar early-neonatal heart regenerative window as mice. Postnatal pig CM growth includes increase in CM length alongside multinucleation, with CM cell cycle arrest and loss of mononucleated-diploid CMs occurring at 2mo-6mo. These CM characteristics are important to consider for pig preclinical studies and may offer opportunities to study aspects of heart regeneration unavailable in other models. |
| Databáze: | OpenAIRE |
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