| Texto completo | |
| Autor(es): Mostrar menos - |
de Mello, Marcela M. Blascke
;
Neves, Viviano Gomes de Oliveira
;
Parente, Juliana Montenegro
;
Pernomian, Laena
;
de Oliveira, Isadora Sousa
;
Pedersoli, Carina Amarante
;
Awata, Wanessa Mayumi Carvalho
;
Tirapelli, Carlos Renato
;
Arantes, Eliane Candiani
;
Tostes, Rita de Cassia A.
;
Schulz, Richard
;
de Castro, Michele Mazzaron
Número total de Autores: 12
|
| Tipo de documento: | Artigo Científico |
| Fonte: | European Journal of Pharmacology; v. 983, p. 9-pg., 2024-09-07. |
| Resumo | |
Aims: Hypertension is associated with an increased activity of matrix metalloproteinase (MMP)-2 in the vasculature, which, in turn, proteolyzes extra- and intracellular proteins that lead to vascular dysfunction. The activity of sarcoplasmic reticulum calcium ATPase (SERCA) is decreased in the aortas of hypertensive rats. Increased activity of MMP-2 proteolyzed SERCA in rat heart during ischemia and reperfusion injury, thus impairing cardiac function. Therefore, we examined whether increased activity of MMP-2 in early hypertension contributes to proteolyze SERCA in the aortas, thus leading to maladaptive vascular remodeling and dysfunction. Main methods: Male Sprague-Dawley rats were submitted to two kidney-one clip (2K-1C) or Sham surgery and treated with doxycycline. Systolic blood pressure (SBP) was assessed by tail-cuff plethysmography. After 7 days, aortas were collected for zymography assays, Western blot to SERCA, ATPase activity assay, vascular reactivity, Ki-67 immunofluorescence and hematoxylin/eosin stain. Key findings: SBP was increased in 2K-1C rats and doxycycline did not reduce it, but decreased MMP-2 activity and prevented SERCA proteolysis in aortas. Cross sectional area, media to lumen ratio and Ki-67 were all increased in the aortas of hypertensive rats and doxycycline decreased Ki-67. In 2K-1C rats, arterial relaxation to acetylcholine was impaired and doxycycline ameliorated it. Significance: doxycycline reduced MMP-2 activity in aortas of 2K-1C rats and prevented proteolysis of SERCA and its dysfunction, thus ameliorating hypertension-induced vascular dysfunction. (AU) | |
| Processo FAPESP: | 19/09174-8 - Ativação extra- e intracelular da metaloproteinase da matriz (MMP)-2 por estresse oxidativo e o remodelamento da hipertensão via mecanismos dependentes e independentes da matriz extracelular |
| Beneficiário: | Michele Mazzaron de Castro |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 21/11936-3 - Centro de Ciência Translacional e Desenvolvimento de Biofármacos |
| Beneficiário: | Benedito Barraviera |
| Modalidade de apoio: | Auxílio à Pesquisa - Centros de Ciência para o Desenvolvimento |
| Processo FAPESP: | 20/13176-3 - Descoberta de anticorpos monoclonais humanos (scFv) com reatividade cruzada e pH-dependentes para as metaloproteases de Bothrops spp |
| Beneficiário: | Isadora Sousa de Oliveira |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 20/02619-1 - Ação proteolítica da metaloproteinase de matriz (MMP)-2 sobre a cálcio ATPase do retículo sarcoplasmático (SERCA) e as alterações vasculares morfofuncionais da Hipertensão Arterial |
| Beneficiário: | Marcela Maria Blascke de Mello |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado Direto |
| 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 |