Search

Your search keyword '"Vagni, S"' showing total 2 results
Start Over Author "Vagni, S" Publisher ivyspring international publisher
2 results on '"Vagni, S"'

1. Stress-induced premature senescence is associated with a prolonged QT interval and recapitulates features of cardiac aging

Author

Lazzarini, E, Lodrini, A, Arici, M, Bolis, S, Vagni, S, Panella, S, Rendon-Angel, A, Saibene, M, Metallo, A, Torre, T, Vassalli, G, Ameri, P, Altomare, C, Rocchetti, M, Barile, L, Lazzarini E., Lodrini A. M., Arici M., Bolis S., Vagni S., Panella S., Rendon-Angel A., Saibene M., Metallo A., Torre T., Vassalli G., Ameri P., Altomare C., Rocchetti M., Barile L., Lazzarini, E, Lodrini, A, Arici, M, Bolis, S, Vagni, S, Panella, S, Rendon-Angel, A, Saibene, M, Metallo, A, Torre, T, Vassalli, G, Ameri, P, Altomare, C, Rocchetti, M, Barile, L, Lazzarini E., Lodrini A. M., Arici M., Bolis S., Vagni S., Panella S., Rendon-Angel A., Saibene M., Metallo A., Torre T., Vassalli G., Ameri P., Altomare C., Rocchetti M., and Barile L.

Abstract

Rationale: Aging in the heart is a gradual process, involving continuous changes in cardiovascular cells, including cardiomyocytes (CMs), namely cellular senescence. These changes finally lead to adverse organ remodeling and resulting in heart failure. This study exploits CMs from human induced pluripotent stem cells (iCMs) as a tool to model and characterize mechanisms involved in aging. Methods and Results: Human somatic cells were reprogrammed into human induced pluripotent stem cells and subsequently differentiated in iCMs. A senescent-like phenotype (SenCMs) was induced by short exposure (3 hours) to doxorubicin (Dox) at the sub-lethal concentration of 0.2 µM. Dox treatment induced expression of cyclin-dependent kinase inhibitors p21 and p16, and increased positivity to senescence-associated beta-galactosidase when compared to untreated iCMs. SenCMs showed increased oxidative stress, alteration in mitochondrial morphology and depolarized mitochondrial membrane potential, which resulted in decreased ATP production. Functionally, when compared to iCMs, SenCMs showed, prolonged multicellular QTc and single cell APD, with increased APD variability and delayed afterdepolarizations (DADs) incidence, two well-known arrhythmogenic indexes. These effects were largely ascribable to augmented late sodium current (INaL) and reduced delayed rectifier potassium current (Ikr). Moreover sarcoplasmic reticulum (SR) Ca2+ content was reduced because of downregulated SERCA2 and increased RyR2-mediated Ca2+ leak. Electrical and intracellular Ca2+ alterations were mostly justified by increased CaMKII activity in SenCMs. Finally, SenCMs phenotype was furtherly confirmed by analyzing physiological aging in CMs isolated from old mice in comparison to young ones. Conclusions: Overall, we showed that SenCMs recapitulate the phenotype of aged primary CMs in terms of senescence markers, electrical and Ca2+ handling properties and metabolic features. Thus, Dox-induced SenCMs can be consider

Published
2022

2. Stress-induced premature senescence is associated with a prolonged QT interval and recapitulates features of cardiac aging.

Author

Lazzarini E, Lodrini AM, Arici M, Bolis S, Vagni S, Panella S, Rendon-Angel A, Saibene M, Metallo A, Torre T, Vassalli G, Ameri P, Altomare C, Rocchetti M, and Barile L

Subjects
Action Potentials, Aged, Animals, Calcium metabolism, Cellular Senescence, Humans, Mice, Myocytes, Cardiac metabolism, Sarcoplasmic Reticulum metabolism, Induced Pluripotent Stem Cells metabolism
Abstract

Rationale: Aging in the heart is a gradual process, involving continuous changes in cardiovascular cells, including cardiomyocytes (CMs), namely cellular senescence. These changes finally lead to adverse organ remodeling and resulting in heart failure. This study exploits CMs from human induced pluripotent stem cells (iCMs) as a tool to model and characterize mechanisms involved in aging. Methods and Results: Human somatic cells were reprogrammed into human induced pluripotent stem cells and subsequently differentiated in iCMs. A senescent-like phenotype (SenCMs) was induced by short exposure (3 hours) to doxorubicin (Dox) at the sub-lethal concentration of 0.2 µM. Dox treatment induced expression of cyclin-dependent kinase inhibitors p21 and p16, and increased positivity to senescence-associated beta-galactosidase when compared to untreated iCMs. SenCMs showed increased oxidative stress, alteration in mitochondrial morphology and depolarized mitochondrial membrane potential, which resulted in decreased ATP production. Functionally, when compared to iCMs, SenCMs showed, prolonged multicellular QTc and single cell APD, with increased APD variability and delayed afterdepolarizations (DADs) incidence, two well-known arrhythmogenic indexes. These effects were largely ascribable to augmented late sodium current (I NaL ) and reduced delayed rectifier potassium current (Ikr). Moreover sarcoplasmic reticulum (SR) Ca 2+ content was reduced because of downregulated SERCA2 and increased RyR2-mediated Ca 2+ leak. Electrical and intracellular Ca 2+ alterations were mostly justified by increased CaMKII activity in SenCMs. Finally, SenCMs phenotype was furtherly confirmed by analyzing physiological aging in CMs isolated from old mice in comparison to young ones. Conclusions: Overall, we showed that SenCMs recapitulate the phenotype of aged primary CMs in terms of senescence markers, electrical and Ca 2+ handling properties and metabolic features. Thus, Dox-induced SenCMs can be considered a novel in vitro platform to study aging mechanisms and to envision cardiac specific anti-aging approach in humans., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Published
2022
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results