Sabbatini Andrea R, Barbaro Natalia R, de Faria Ana Paula, Modolo Rodrigo, Ritter Alessandra Mileni V, Pinho Claudio, Amorim Rivadavio Fernandes Batista, Fontana Vanessa, Moreno Heitor
Laboratory of Cardiovascular Pharmacology, Faculty of Medical Sciences and Teaching Hospital, University of Campinas (Unicamp), Campinas, Sao Paulo, Brazil.
Faculty of Medicine, Pontifical Catholic University of Campinas (Puccamp), Campinas, Sao Paulo, Brazil.
J Clin Hypertens (Greenwich). 2016 Oct;18(10):969-975. doi: 10.1111/jch.12865. Epub 2016 Jul 14.
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.
顽固性高血压(RH)与器官损害和心血管风险相关。有证据表明基质金属蛋白酶2(MMP-2)和金属蛋白酶组织抑制剂2(TIMP-2)参与高血压及心血管重塑过程。本研究旨在评估RH患者中MMP-2和TIMP-2的水平及其与包括动脉僵硬度和心脏肥大在内的器官损害之间的关系。比较了19例血压正常(NT)患者、116例非顽固性高血压(HTN)患者和116例顽固性HTN(RH)患者的MMP-2和TIMP-2水平。NT、HTN和RH组之间的MMP-2水平无差异,而RH组的TIMP-2水平高于HTN组和NT组(分别为90.0 [76.1 - 107.3] vs 70.1 [57.7 - 88.3] vs 54.7 [40.9 - 58.1] ng/mL,P <.01)。与HTN组和NT组相比,RH组的MMP-2/TIMP-2比值降低(分别为2.7 [1.9 - 3.4] vs 3.3 [2.6 - 4.2] vs 4.9 [4.5 - 5.3],P <.01)。在RH组和HTN组中,未发现MMP-2水平、TIMP-2及MMP-2/TIMP-2比值与心脏肥大和动脉僵硬度之间存在关联。最后,在回归分析中,MMP-2/TIMP-2比值降低和TIMP-2水平升高与RH独立相关。本研究结果提供了证据表明TIMP-2与RH相关,可能是筛查RH患者的一个潜在生物标志物。