Increased activity of matrix metalloproteinase (MMP)-2 contributes to recycle type I collagen to contribute to hypertrophic arterial remodeling in renovascular hypertension

Increased activity of matrix metalloproteinase (MMP)-2 contributes to recycle type I collagen to contribute to hypertrophic arterial remodeling in renovascular hypertension

• Autor
• Viviano Gomes de Oliveira Neves
• Co-autores
• Marcela Maria Blascke de Mello , Pedro Henrique Leite da Silva , Laena Pernomiam , Juliana Montenegro Parente , Michele Mazzaron de Castro
• Resumo

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  Data from our group showed increased proliferation of vascular smooth muscle cells (VSMC) in the aorta of two kidney-one clip (2K1C) rats at first week of hypertension, and this effect was reduced after administration of doxycycline¹. Type I collagen (COL-1) proteolytic products contribute to VSMC proliferation via integrin receptor and focal adhesion kinase (FAK) activation. We evaluated whether the early activation of MMP-2 in hypertension induces VSMC proliferation due to COL-1 proteolysis, which may activate integrin and FAK to develop hypertrophic arterial remodeling. Rats were submitted to 2K1C surgery to induce hypertension and they were orally treated with doxycycline or vehicle (five days at first week and eight weeks at ten weeks of hypertension) (CEUA-USP 165/2019). In aorta, we evaluated MMP-2 and COL-1 expression by Western blotting; MMP-2 activity by gelatin and in situ zymography, and collagen deposition by picrosirius red. Two-way ANOVA followed by Tukey post hoc test with p<0.05 was done. 2K1C rats developed high systolic blood pressure at first week (156 ± 13 mmHg vs. Sham p<0,001), which was progressively higher at ten weeks (219 ± 6 mmHg, p<0,0001). MMP-2 expression and activity were increased in 2K1C rats at first and tenth weeks of hypertension (p<0.05). Doxycycline reduced MMP-2 activity only in the acute situation (p<0.05). The 2K1C rats had increased levels of COL-1 as well as its potential degradation products (p<0.05) in the aortas at first week. However, the deposition of collagen was notably resynthesized in the aortas of chronic 2K1C rats (p<0.05). We concluded that increased activity of MMP-2 may contribute to COL-1 proteolysis in aortas at early stages of hypertension, with its potential re-synthesis at late stages. This proteolytic effect of MMP-2 on collagen may contribute to stimulate VSMCs proliferation through integrins and FAK. The mechanisms are currently being investigating.

   

• Palavras-chave
• MMP-2; Type I Collagen (COL-1); remodeling; aorta; hypertension
• Modalidade
• Comunicação oral
• Área Temática
• Sinalização celular