title: Matrix metalloproteinase (MMP)-2 decreases calponin-1 levels and contributes to arterial remodeling in early hypertension.
abstract: 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 30mg/kg/day. Systolic blood pressure was increased in the 2K1C rats after 1 and 2weeks post-surgery, and doxycycline was effective to reduce it only at 2weeks of hypertension (p<0.05). Increased activity of MMP-2 was observed in aortas from 2K1C at 1 and 2weeks 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 1week of hypertension, and it was established by 2weeks. 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 1week of hypertension, and doxycycline prevented its loss (p<0.05). However, at 2weeks 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 1week of hypertension. MMP-2 may contribute to the post-translational decrease in calponin-1, thus culminating in hypertension-induced maladaptive arterial remodeling.
authors.affiliation: Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Av. Bandeirantes, 3900, 14049-900, Ribeirao Preto, SP, Brazil.
authors.forename: Vanessa de Almeida
authors.initials: VA
authors.lastname: Belo
authors.affiliation: Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Av. Bandeirantes, 3900, 14049-900, Ribeirao Preto, SP, Brazil.
authors.forename: Juliana Montenegro
authors.initials: JM
authors.lastname: Parente
authors.affiliation: Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Av. Bandeirantes, 3900, 14049-900, Ribeirao Preto, SP, Brazil.
authors.forename: José Eduardo
authors.initials: JE
authors.lastname: Tanus-Santos
authors.affiliation: Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Av. Bandeirantes, 3900, 14049-900, Ribeirao Preto, SP, Brazil. Electronic address: castro@fmrp.usp.br.
authors.forename: Michele M
authors.initials: MM
authors.lastname: Castro
mesh_terms: D000818:Animals; D001011:Aorta; D001158:Arteries / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D003600:Cytosol / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism; D058246:Prehypertension / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D059748:Proteolysis; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D017208:Rats, Wistar; D015534:Trans-Activators / Q000378:metabolism; D066253:Vascular Remodeling; D000096985:Calponins; D000099251:Myocardin
chemical_list: D015415:Biomarkers; D002135:Calcium-Binding Proteins; D020778:Matrix Metalloproteinase 2; D008840:Microfilament Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D000096985:Calponins; D000099251:Myocardin; C522363:Mmp2 protein, rat
keywords: Arterial hypertension; Calponin-1; Matrix metalloproteinase-2; Vascular remodeling