| Texto completo | |
| Autor(es): |
Feltran, Georgia da Silva
;
dos Santos, Emerson Araujo Alves
;
Andrade, Amanda Fantini de Camargo
;
Zambuzzi, Willian Fernando
;
da Silva, Rodrigo Augusto Foganholi
Número total de Autores: 5
|
| Tipo de documento: | Artigo Científico |
| Fonte: | Experimental Cell Research; v. 443, n. 1, p. 10-pg., 2024-11-01. |
| Resumo | |
In light of the complex origins of ectopic vascular calcification and its significant health implications, this study offers a comprehensive exploration of the molecular dynamics governing vascular smooth muscle cells (VSMCs). Focusing on epigenetic modulation, we investigate the transition from a contractile to a calcifying phenotype in VSMCs, with an emphasis on understanding the role of SIRT1. For this purpose, a single batch of human aortic SMCs, used at a specified passage number to maintain consistency, was subjected to calcium and phosphate overload for up to 72 h. Our findings, validated through RT q-PCR, Western blot, immunofluorescence, and DNA methylation analyses, reveal a complex interplay between acetyltransferases and deacetylases during this phenotypic transition. We highlight HAT1A's critical role in histone acetylation regulation and the involvement of HDACs, as evidenced by subcellular localization studies. Moreover, we demonstrate the modulation of SIRT1 expression, a class III deacetylase, during VSMC calcification, underscoring the influence of DNA methylation in this process. Importantly, the study addresses previously unexplored aspects of the dynamic protein expression patterns observed, providing insight into the counterintuitive expressions of key proteins such as Runx2 and osterix. This research underscores the significant impact of epigenetic mechanisms, particularly the modulation of SIRT1, in the transition from a contractile to a calcifying phenotype in VSMCs, offering potential avenues for further exploration in the context of vascular calcification. (AU) | |
| Processo FAPESP: | 14/22689-3 - Sinalização parácrina mediada por microvesículas e proteínas entre células ósseas e endoteliais durante o desenvolvimento e regeneração do tecido ósseo |
| Beneficiário: | Willian Fernando Zambuzzi |
| Modalidade de apoio: | Auxílio à Pesquisa - Jovens Pesquisadores |
| Processo FAPESP: | 19/26854-2 - Efeito de um modelo de hipóxia no acoplamento angiogênese-osteogênese: um olhar às microvesículas e potenciais aplicações biotecnológicas |
| Beneficiário: | Willian Fernando Zambuzzi |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 19/22255-7 - Marcadores osteogênicos e reprogramação epigenética durante a transição fenotípica do músculo liso vascular: da contração à calcificação |
| Beneficiário: | Geórgia da Silva Feltran |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado |