title: Increased Circulating Tissue Inhibitor of Metalloproteinase-2 Is Associated With Resistant Hypertension.
abstract: Resistant hypertension (RH) is associated with organ damage and cardiovascular risk. Evidence suggests the involvement of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinase 2 (TIMP-2) in hypertension and in cardiovascular remodeling. The aim of this study was to assess the levels of MMP-2 and TIMP-2 in RH and its relation with organ damage, including arterial stiffness and cardiac hypertrophy. MMP-2 and TIMP-2 levels were compared among 19 patients with normotension (NT), 116 with nonresistant hypertension (HTN) and 116 patients with resistant HTN (RH). MMP-2 levels showed no differences among NT, HTN, and RH groups, while TIMP-2 levels were higher in RH compared with HTN and NT groups (90.0 [76.1-107.3] vs 70.1 [57.7-88.3] vs 54.7 [40.9-58.1] ng/mL, P<.01), respectively. MMP-2/TIMP-2 ratio was reduced in the RH group compared with the HTN and NT groups (2.7 [1.9-3.4] vs 3.3 [2.6-4.2] vs 4.9 [4.5-5.3], P<.01), respectively. No associations were found between MMP-2 levels, TIMP-2, and MMP-2/TIMP-2 ratio with cardiac hypertrophy and arterial stiffness in the RH and HTN groups. Finally, in a regression analysis, reduced MMP-2/TIMP-2 ratio and increased TIMP-2 levels were independently associated with RH. The present findings provide evidence that TIMP-2 is associated with RH and might be a possible biomarker for screening RH patients.
authors.affiliation: Laboratory of Cardiovascular Pharmacology, Faculty of Medical Sciences and Teaching Hospital, University of Campinas (Unicamp), Campinas, Sao Paulo, Brazil.
authors.forename: Andrea R
authors.initials: AR
authors.lastname: Sabbatini
authors.affiliation: Laboratory of Cardiovascular Pharmacology, Faculty of Medical Sciences and Teaching Hospital, University of Campinas (Unicamp), Campinas, Sao Paulo, Brazil.
authors.forename: Natalia R
authors.initials: NR
authors.lastname: Barbaro
authors.affiliation: Laboratory of Cardiovascular Pharmacology, Faculty of Medical Sciences and Teaching Hospital, University of Campinas (Unicamp), Campinas, Sao Paulo, Brazil.
authors.forename: Ana Paula
authors.identifier: 0000-0001-8585-7238
authors.initials: AP
authors.lastname: de Faria
authors.affiliation: Laboratory of Cardiovascular Pharmacology, Faculty of Medical Sciences and Teaching Hospital, University of Campinas (Unicamp), Campinas, Sao Paulo, Brazil.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Modolo
authors.affiliation: Laboratory of Cardiovascular Pharmacology, Faculty of Medical Sciences and Teaching Hospital, University of Campinas (Unicamp), Campinas, Sao Paulo, Brazil.
authors.forename: Alessandra Mileni V
authors.initials: AM
authors.lastname: Ritter
authors.affiliation: Faculty of Medicine, Pontifical Catholic University of Campinas (Puccamp), Campinas, Sao Paulo, Brazil.
authors.forename: Claudio
authors.initials: C
authors.lastname: Pinho
authors.affiliation: Laboratory of Neuromodulation & Center for Clinical Research Learning, Department of Physical Medicine and Rehabilitation (PM&R), Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, MA.
authors.forename: Rivadavio Fernandes Batista
authors.initials: RF
authors.lastname: Amorim
authors.affiliation: Laboratory of Cardiovascular Pharmacology, Faculty of Medical Sciences and Teaching Hospital, University of Campinas (Unicamp), Campinas, Sao Paulo, Brazil.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Fontana
authors.affiliation: Laboratory of Cardiovascular Pharmacology, Faculty of Medical Sciences and Teaching Hospital, University of Campinas (Unicamp), Campinas, Sao Paulo, Brazil. hmoreno@uol.com.br, deia_sabbatini@hotmail.com.
authors.forename: Heitor
authors.initials: H
authors.lastname: Moreno
mesh_terms: D000368:Aged; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000201:enzymology* / Q000503:physiopathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood*; D008875:Middle Aged; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood*; D015854:Up-Regulation; D059289:Vascular Stiffness; D020257:Ventricular Remodeling
chemical_list: C560823:TIMP2 protein, human; D019716:Tissue Inhibitor of Metalloproteinase-2; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2