Nombre: NINA BRUNA DE SOUZA MAWANDJI
Fecha de publicación: 28/03/2025
Junta de examinadores:
Nombre |
Papel |
|---|---|
| ARICLÉCIO CUNHA DE OLIVEIRA | Examinador Externo |
| LEONARDO DOS SANTOS | Examinador Interno |
Sumario: Introduction: Copper is an essential metal for the body's development and function.
However, scientific evidence indicates that elevated levels are associated with an
increased risk of cardiovascular diseases, including changes in vascular reactivity and
elevated blood pressure. Despite this, the literature has yet to present studies
demonstrating whether such disturbances also involve alterations in the functions of
perivascular adipose tissue (PVAT). Objective: To investigate the effects of chronic
copper overload on the secretory function of mesenteric PVAT, with an emphasis on
markers of vascular regulation. Methods: In the first phase, 8-week-old male Wistar
rats were assigned to two groups: Control (saline, i.p.) or Copper (25.72 g/kg/day of
Cu, i.p., for 30 days). In the second phase, the rats were divided into four groups:
Control (saline, i.p., water by gavage), Copper (Cu, i.p., water by gavage), Losartan
(saline, i.p., 10 mg/kg/day of Losartan by gavage), or Copper + Losartan (Cu, i.p., 10
mg/kg/day of Losartan by gavage). Mesenteric PVAT was collected for adipocyte
morphometric analysis, gene and protein expression of inflammatory and
vasoregulatory molecules, renin-angiotensin system components, quantification of
reactive species, and antioxidant enzyme activity. Blood/serum samples were used for
biochemical and hormonal analyses. Results: In mesenteric PVAT, copper overload
increased adipocyte diameter and secretion of TNF- and PAI-1, while reducing IL-10
levels and basal lipolysis. It also upregulated mRNA levels of MCP-1, F4/80, CD86,
arginase-1, iNOS, TLR4, ACE1, and AT1R. Additionally, copper administration
increased reactive oxygen species and decreased SOD protein expression, while
elevating serum Ang II concentrations. When copper overload was administered
concomitantly with Losartan, there was an attenuation in TNF- production and in the
gene expression of the TLR4 receptor and arginase-1. Conclusion: A 30-day copper
overload induces alterations in the secretory function of mesenteric artery PVAT in
rats, characterized by increased production of pro-inflammatory adipokines, activation
of inflammatory responses, and oxidative stress via the TLR4-AT1R-Ang II axis.
