| Full text | |
| Author(s): Show less - |
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
Total Authors: 12
|
| Document type: | Journal article |
| Source: | European Journal of Pharmacology; v. 983, p. 9-pg., 2024-09-07. |
| Abstract | |
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) | |
| FAPESP's process: | 19/09174-8 - Extra- and intracellular activation of matrix metalloproteinase-2 by oxidative stress in arterial hypertension-induced vascular remodeling via extracellular matrix dependent- and independent mechanisms |
| Grantee: | Michele Mazzaron de Castro |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 21/11936-3 - Center for Translational Science and Biopharmaceutical Development |
| Grantee: | Benedito Barraviera |
| Support Opportunities: | Research Grants - Science Centers for Development |
| FAPESP's process: | 20/13176-3 - Human monoclonal antibodies (scFv) discovery with cross-reactivity and pH-dependent to metalloproteases from Bothrops spp |
| Grantee: | Isadora Sousa de Oliveira |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 20/02619-1 - Potential effects of matrix metalloproteinase (MMP)-2 on the sarcoplasmic reticulum calcium ATPase (SERCA) in Hypertension-induced vascular dysfunction |
| Grantee: | Marcela Maria Blascke de Mello |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |
| FAPESP's process: | 22/04888-5 - Gestational and neonatal treatment with antioxidant or interleukin-10 decreases maladaptive arterial remodeling and Hypertension in the adult offspring of hypertensive rats through downregulating inflammatory mediators and MMP-2 activity |
| Grantee: | Michele Mazzaron de Castro |
| Support Opportunities: | Regular Research Grants |