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| Author(s): |
Camila Stephanie Balbino Silva
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) |
| Defense date: | 2022-03-07 |
| Examining board members: |
Gabriela Placoná Diniz;
Eliana Hiromi Akamine;
Daniella Bonaventura;
Ana Paula Couto Davel
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| Advisor: | Gabriela Placoná Diniz; Luciana Venturini Rossoni |
| Abstract | |
The adipose tissue accumulation observed in overweight and obesity promotes changes in the blood vessels, leading to impaired vascular function. Blood vessels are surrounded by perivascular adipose tissue (PVAT), which plays an important role in the local regulation of vascular tone by opposing contractile stimuli. Physiologically, PVAT produces and releases several vasoactive molecules such as adipokines, miRNAs, and nitric oxide. The imbalance of these factors may be related to the vascular dysfunction observed in obese individuals. Recent studies have evidenced that miRNA-22 (miR-22) increases pro-inflammatory cytokine expression in endothelial cells and reduces the proliferative state of vascular smooth muscle cells. Previous works from our laboratory demonstrated that the miR-22 deletion attenuated the increase in the expression of inflammatory genes in the white adipose tissue and increased the thermogenic genes expression in the brown adipose tissue of obese mice. Despite these findings, the function of miR-22 in vascular reactivity as well as in the influence of PVAT on this response is unknown. Thus, the aim of this work was to investigate the role of miR-22 in thoracic aortic vascular reactivity and PVAT function. WT and KO mice for miR-22 were fed a control or high-fat diet for 16 weeks. We observed that the absence of miR-22 reduced the contraction to noradrenaline, via a NOS-dependent mechanism, and loss of the PVAT anti contractile effect with an increase in the formation of 4-HNE, indicating a possible oxidative stress in this tissue. Furthermore, the model used for inducing obesity was effective, since mice fed a high-fat diet showed increased adiposity, insulin resistance, glucose intolerance, and reduced contraction to noradrenaline and NOS-mediated anticontractile effect of PVAT. Finally, we observed that PVAT from KO mice for miR-22 fed a high-fat diet presented increased expression of nNOS, reduced activation of eNOS and improved NOS-induced PVAT anticontractile effect. Thus, the data indicate that miR-22 is important for maintaining vascular function. (AU) | |
| FAPESP's process: | 18/26657-0 - Impact of miRNA-22 in the vascular reactivity of obese mice |
| Grantee: | Camila Stephanie Balbino Silva |
| Support Opportunities: | Scholarships in Brazil - Master |