Matrix metalloproteinase (MMP)-2 decreases calponin-1 levels and contributes to arterial remodeling in early hypertension

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• 作者：Vanessa de Almeida Belo ; Juliana Montenegro Parente ; José ; Eduardo Tanus-Santos ; Michele M. Castro ; ^{castro@fmrp.usp.br" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Matrix metalloproteinase-2 ; Arterial hypertension ; Vascular remodeling ; Calponin-1
• 刊名：Biochemical Pharmacology
• 出版年：2016
• 出版时间：15 October 2016
• 年：2016
• 卷：118
• 期：Complete
• 页码：50-58
• 全文大小：2226 K

文摘

Increased matrix metalloproteinase (MMP)-2 is implicated in the vascular remodeling of hypertension. Calponin-1 is a contractile protein, and its absence is associated with vascular smooth muscle cell (VSMC) phenotype switch, which leads to migration and remodeling. We evaluated whether increased MMP-2 activity precedes chronic vascular remodeling by decreasing calponin-1 and inducing VSMC proliferation. Sham or two kidney-one clip (2K1C) rats were treated with doxycycline at 30 mg/kg/day. Systolic blood pressure was increased in the 2K1C rats after 1 and 2 weeks post-surgery, and doxycycline was effective to reduce it only at 2 weeks of hypertension (p < 0.05). Increased activity of MMP-2 was observed in aortas from 2K1C at 1 and 2 weeks of hypertension, followed by increased VSMC proliferation, and those effects were abolished by treating 2K1C rats with doxycycline (p < 0.05). Increased aortic media to lumen ratio started to emerge in 2K1C rats at 1 week of hypertension, and it was established by 2 weeks. MMP-2 and calponin-1 co-localized in the cytosol of VSMC. Aortas from 2K1C rats showed a significant reduction in calponin-1 levels at 1 week of hypertension, and doxycycline prevented its loss (p < 0.05). However, at 2 weeks of hypertension, calponin-1 was upregulated in 2K1C (p < 0.05 vs. Sham groups). The mRNA levels of calponin-1 were not altered in the aortas of 2K1C at 1 week of hypertension. MMP-2 may contribute to the post-translational decrease in calponin-1, thus culminating in hypertension-induced maladaptive arterial remodeling.