| Texto completo | |
| Autor(es): |
Morgado, Leticia Aparecida Lopes
;
Rodrigues, Larissa Maria Zacarias
;
Silva, Daiane Cristina Floriano
;
da Silva, Bruno Durante
;
Irigoyen, Maria Claudia Costa
;
Takano, Ana Paula Cremasco
Número total de Autores: 6
|
| Tipo de documento: | Artigo Científico |
| Fonte: | BIOMEDICINES; v. 13, n. 1, p. 14-pg., 2025-01-01. |
| Resumo | |
Background/Objectives: Aging is associated with structural and functional changes in the heart, including hypertrophy, fibrosis, and impaired contractility. Cellular mechanisms such as senescence, telomere shortening, and DNA damage contribute to these processes. Nuclear factor kappa B (NF-kappa B) has been implicated in mediating cellular responses in aging tissues, and increased NF-kappa B expression has been observed in the hearts of aging rodents. Therefore, NF-kappa B is suspected to play an important regulatory role in the cellular and molecular processes occurring in the heart during aging. This study investigates the in vivo role of NF-kappa B in aging-related cardiac alterations, focusing on senescence and associated cellular events. Methods: Young and old wild-type (WT) and transgenic male mice with cardiomyocyte-specific NF-kappa B suppression (3M) were used to assess cardiac function, morphology, senescence markers, lipofuscin deposition, DNA damage, and apoptosis. Results: Kaplan-Meier analysis revealed reduced survival in 3M mice compared to WT. Echocardiography showed evidence of eccentric hypertrophy, and both diastolic and systolic dysfunction in 3M mice. Both aged WT and 3M mice exhibited cardiac hypertrophy, with more pronounced hypertrophic changes in cardiomyocytes from 3M mice. Additionally, cardiac fibrosis, senescence-associated beta-galactosidase activity, p21 protein expression, and DNA damage (marked by phosphorylated H2A.X) were elevated in aged WT and both young and aged 3M mice. Conclusions: The suppression of NF-kappa B in cardiomyocytes leads to pronounced cardiac remodeling, dysfunction, and cellular damage associated with the aging process. These findings suggest that NF-kappa B plays a critical regulatory role in cardiac aging, influencing both cellular senescence and molecular damage pathways. This has important implications for the development of therapeutic strategies aimed at mitigating age-related cardiovascular diseases. (AU) | |
| Processo FAPESP: | 19/06435-5 - Mecanismos celulares e moleculares envolvidos no envelhecimento cardíaco: efeitos da supressão específica de NF-kB em cardiomiócitos |
| Beneficiário: | Ana Paula Cremasco Takano |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 19/26085-9 - Avaliação do papel de NF-kB em mecanismos associados ao envelhecimento cardíaco induzido por D-galactose |
| Beneficiário: | Letícia Aparecida Lopes Morgado |
| Modalidade de apoio: | Bolsas no Brasil - Iniciação Científica |
| Processo FAPESP: | 19/26357-9 - Comparação de modelos de envelhecimento natural e induzido por D-galactose no estudo de senescência do tecido cardíaco |
| Beneficiário: | Larissa Maria Zacarias Rodrigues |
| Modalidade de apoio: | Bolsas no Brasil - Iniciação Científica |