title: Matrix Metalloproteinase-2 Activity is Associated with Divergent Regulation of Calponin-1 in Conductance and Resistance Arteries in Hypertension-induced Early Vascular Dysfunction and Remodelling.
abstract: Matrix metalloproteinase (MMP)-2 participates in hypertension-induced maladaptive vascular remodelling by degrading extra- and intracellular proteins. The consequent extracellular matrix rearrangement and phenotype switch of vascular smooth muscle cells (VSMCs) lead to increased cellular migration and proliferation. As calponin-1 degradation by MMP-2 may lead to VSMC proliferation during hypertension, the hypothesis of this study is that increased MMP-2 activity contributes to early hypertension-induced maladaptive remodelling in conductance and resistance arteries via regulation of calponin-1. The main objective was to analyse whether MMP-2 exerts similar effects on the structure and function of the resistance and conductance arteries during early hypertension. Two-kidney, one-clip (2K-1C) hypertensive male rats and corresponding controls were treated with doxycycline (30 mg/kg/day) or water until reaching one week of hypertension. Systolic blood pressure was increased in 2K-1C rats, and doxycycline did not reduce it. Aortas and mesenteric arteries were analysed. MMP-2 activity and expression were increased in both arteries, and doxycycline reduced it. Significant hypertrophic remodelling and VSMC proliferation were observed in aortas but not in mesenteric arteries of 2K-1C rats. The contractility of mesenteric arteries to phenylephrine was increased in 2K-1C rats, and doxycycline prevented this alteration. The potency of phenylephrine to contract aortas of 2K-1C rats was increased, and doxycycline decreased it. Whereas calponin-1 expression was increased in 2K-1C mesenteric arteries, calponin-1 was reduced in aortas. Doxycycline treatment reverted changes in calponin-1 expression. MMP-2 contributes to hypertrophic remodelling in aortas by decreasing calponin-1 levels, which may result in VSMC proliferation. On the other hand, MMP-2-dependent increased calponin-1 in mesenteric arteries may contribute to vascular hypercontractility in 2K-1C rats. Divergent regulation of calponin-1 by MMP-2 may be an important mechanism that leads to maladaptive vascular effects in hypertension.
authors.affiliation: Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Juliana M
authors.initials: JM
authors.lastname: Parente
authors.affiliation: Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Camila A
authors.initials: CA
authors.lastname: Pereira
authors.affiliation: Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Gustavo H
authors.initials: GH
authors.lastname: Oliveira-Paula
authors.affiliation: Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: José E
authors.initials: JE
authors.lastname: Tanus-Santos
authors.affiliation: Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Rita C
authors.initials: RC
authors.lastname: Tostes
authors.affiliation: Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Michele M
authors.initials: MM
authors.lastname: Castro
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006978:Hypertension, Renovascular / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D008638:Mesenteric Arteries / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D008840:Microfilament Proteins / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D032389:Myocytes, Smooth Muscle / Q000201:enzymology / Q000473:pathology; D017208:Rats, Wistar; D015398:Signal Transduction; D066253:Vascular Remodeling / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D000096985:Calponins
chemical_list: D002135:Calcium-Binding Proteins; D020778:Matrix Metalloproteinase 2; D008840:Microfilament Proteins; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000096985:Calponins; C522363:Mmp2 protein, rat