| Texto completo | |
| Autor(es): |
Ramos, Luan Victor Resque
;
de Mello, Marcela M. Blascke
;
de Melo, Bruno Marcel Silva
;
de Oliveira Neto, Jose Teles
;
Bueno, Evellin Karina Pires
;
Alves Filho, Jose Carlos Farias
;
Tostes, Rita
;
Castro, Michele M.
Número total de Autores: 8
|
| Tipo de documento: | Artigo Científico |
| Fonte: | VASCULAR PHARMACOLOGY; v. 160, p. 9-pg., 2025-09-01. |
| Resumo | |
Angiotensin II (Ang II) increases C3a effects through its receptors, promoting aortic oxidative stress and upregulating matrix metalloproteinase (MMP)-2. MMP-2 is implicated in hypertrophic arterial remodeling in hypertension. This study investigated whether C3a receptor activation contributes to oxidative stress and increased MMP-2 activity in aortas of Ang II treated mice, ultimately leading to maladaptive vascular changes. Hypertension was induced in C57BL/6 mice via subcutaneous implantation of osmotic mini pumps delivering Ang II (1000 ng/kg/min) for 14 days. Mice were administered the C3aR antagonist, SB290157 (1 mg/kg/day, intraperitoneally) every other day for 14 days. Systolic blood pressure (SBP) and vascular function were assessed via direct blood pressure measurements and contraction and relaxation analysis in a wire myography. Aortic MMP-2 activity was analyzed by gel and in situ zymography. SB290157 did not decrease SBP, aortic hypertrophy or increased aortic reactivity to phenylephrine in Ang II treated mice. Ang II exhibited higher levels of C3a in the plasma and increased tumor necrose factor (TNF)-alpha and interleukin (IL)-6 in the kidneys (*p < 0.05). SB290157 did not alter C3a, but reduced TNF-alpha and IL-6 in hypertension (#p < 0.05 vs. Ang II). SB290157 also decreased aortic oxidative stress and p65 factor nuclear kappa B (NFkB) in Ang II treated mice (*p < 0.05). MMP-2 activity was increased in the aortas of Ang II (*p < 0.05) and SB290157 decreased it (*p < 0.05). Pharmacological antagonism of C3a receptor attenuates oxidative stress and MMP-2 activity in the aortas of Ang II treated mice. (AU) | |
| Processo FAPESP: | 23/04177-4 - Aumento no sistema complemento e redução de células T reguladoras podem aumentar a atividade da metaloproteinase de matriz (MMP)-2 e o remodelamento arterial na hipertensão |
| Beneficiário: | Luan Victor Resque Ramos |
| Modalidade de apoio: | Bolsas no Brasil - Mestrado |
| Processo FAPESP: | 22/04888-5 - Antioxidante e modulação imunológica nas fases gestacional e neonatal reduzem o remodelamento arterial hipertrófico e a Hipertensão na prole adulta de ratos hipertensos por diminuir fatores inflamatórios e a atividade da MMP-2 |
| Beneficiário: | Michele Mazzaron de Castro |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |