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Fibulin-3 may improve vascular health through inhibition of MMP-2/9 and oxidative stress in spontaneously hypertensive rats

Fibulin-3 has been suggested to function in the remodeling of the extracellular matrix, however its role remains unclear in hypertensive vascular remodeling. In the current study, 10 Wistar-Kyoto (WKY) rats (control group) and 30 spontaneously hypertensive rats (SHRs) were used. SHRs were randomized...

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Autores principales: LIN, ZHONGWEI, WANG, ZHUO, LI, GUOBIAO, LI, BOWEI, XIE, WENLIN, XIANG, DINGCHENG
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4838143/
https://www.ncbi.nlm.nih.gov/pubmed/27035767
http://dx.doi.org/10.3892/mmr.2016.5036
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author LIN, ZHONGWEI
WANG, ZHUO
LI, GUOBIAO
LI, BOWEI
XIE, WENLIN
XIANG, DINGCHENG
author_facet LIN, ZHONGWEI
WANG, ZHUO
LI, GUOBIAO
LI, BOWEI
XIE, WENLIN
XIANG, DINGCHENG
author_sort LIN, ZHONGWEI
collection PubMed
description Fibulin-3 has been suggested to function in the remodeling of the extracellular matrix, however its role remains unclear in hypertensive vascular remodeling. In the current study, 10 Wistar-Kyoto (WKY) rats (control group) and 30 spontaneously hypertensive rats (SHRs) were used. SHRs were randomized into three groups: The placebo group, intravenous (I.V.) physiological saline; the FBLN-1 group, low-dose fibulin-3 protein (I.V.; 120 ng/kg); and the FBLN-2 group, high-dose fibulin-3 protein (I.V.; 240 ng/kg). Histological analysis was used to analyze vascular remodeling. The expression of fibulin-3, matrix metalloproteinase (MMP)-2, MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-3 were detected by immunohistochemistry, western blotting and reverse transcription-quantitative polymerase chain reaction. Oxidative stress was detected by dihydroethidium staining. The systolic blood pressure (SBP) of SHRs was observed to be significantly greater than that of WKY rats (P<0.05). SBP in the FBLN-2 group was significantly reduced compared with the placebo group (182±12 mmHg vs. 224±14 mmHg; P<0.05). The thoracic aortic wall thickness in the SHR groups (placebo group, FBLN-1 group and FBLN-2 group) was observed to tbe significantly thicker than in the control group (P<0.01). The wall thickness of the FBLN-2 group was significantly greater than that of the placebo and FBLN-1 groups (124.2±11.8 μm vs. 106.9±9.5 μm and 96.8±10.2 μm; P<0.05). The wall-to-lumen ratios of the placebo, FBLN-1 and FBLN-2 groups were significantly greater than that of the control group (P<0.05). In addition, the expression levels of fibulin-3 and MMP-2/9 at protein and mRNA levels were significantly increased in the thoracic aorta of the placebo group compared with the control group (P<0.05). The levels of MMP-2/9 were significantly reduced in the FBLN-2 group compared with the placebo group (P<0.05). Levels of TIMP-3 however, exhibited no significant differences in the four groups (P>0.05). Reactive oxygen species (ROS) were increased in the placebo group vs. the control group. Fibulin-3 was able to alleviate the levels of ROS in the FBLN groups. It is suggested that fibulin-3 may act as a growth factor in the arteries. In addition, the results indicated that fibulin-3 may reduce the levels of MMP-2 and -9 and oxidative stress in hypertensive vascular remodeling. Upregulating fibulin-3 may be beneficial for improving vascular health and offsetting certain cardiovascular risk factors of hypertension.
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spelling pubmed-48381432016-04-21 Fibulin-3 may improve vascular health through inhibition of MMP-2/9 and oxidative stress in spontaneously hypertensive rats LIN, ZHONGWEI WANG, ZHUO LI, GUOBIAO LI, BOWEI XIE, WENLIN XIANG, DINGCHENG Mol Med Rep Articles Fibulin-3 has been suggested to function in the remodeling of the extracellular matrix, however its role remains unclear in hypertensive vascular remodeling. In the current study, 10 Wistar-Kyoto (WKY) rats (control group) and 30 spontaneously hypertensive rats (SHRs) were used. SHRs were randomized into three groups: The placebo group, intravenous (I.V.) physiological saline; the FBLN-1 group, low-dose fibulin-3 protein (I.V.; 120 ng/kg); and the FBLN-2 group, high-dose fibulin-3 protein (I.V.; 240 ng/kg). Histological analysis was used to analyze vascular remodeling. The expression of fibulin-3, matrix metalloproteinase (MMP)-2, MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-3 were detected by immunohistochemistry, western blotting and reverse transcription-quantitative polymerase chain reaction. Oxidative stress was detected by dihydroethidium staining. The systolic blood pressure (SBP) of SHRs was observed to be significantly greater than that of WKY rats (P<0.05). SBP in the FBLN-2 group was significantly reduced compared with the placebo group (182±12 mmHg vs. 224±14 mmHg; P<0.05). The thoracic aortic wall thickness in the SHR groups (placebo group, FBLN-1 group and FBLN-2 group) was observed to tbe significantly thicker than in the control group (P<0.01). The wall thickness of the FBLN-2 group was significantly greater than that of the placebo and FBLN-1 groups (124.2±11.8 μm vs. 106.9±9.5 μm and 96.8±10.2 μm; P<0.05). The wall-to-lumen ratios of the placebo, FBLN-1 and FBLN-2 groups were significantly greater than that of the control group (P<0.05). In addition, the expression levels of fibulin-3 and MMP-2/9 at protein and mRNA levels were significantly increased in the thoracic aorta of the placebo group compared with the control group (P<0.05). The levels of MMP-2/9 were significantly reduced in the FBLN-2 group compared with the placebo group (P<0.05). Levels of TIMP-3 however, exhibited no significant differences in the four groups (P>0.05). Reactive oxygen species (ROS) were increased in the placebo group vs. the control group. Fibulin-3 was able to alleviate the levels of ROS in the FBLN groups. It is suggested that fibulin-3 may act as a growth factor in the arteries. In addition, the results indicated that fibulin-3 may reduce the levels of MMP-2 and -9 and oxidative stress in hypertensive vascular remodeling. Upregulating fibulin-3 may be beneficial for improving vascular health and offsetting certain cardiovascular risk factors of hypertension. D.A. Spandidos 2016-05 2016-03-21 /pmc/articles/PMC4838143/ /pubmed/27035767 http://dx.doi.org/10.3892/mmr.2016.5036 Text en Copyright: © Lin et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
LIN, ZHONGWEI
WANG, ZHUO
LI, GUOBIAO
LI, BOWEI
XIE, WENLIN
XIANG, DINGCHENG
Fibulin-3 may improve vascular health through inhibition of MMP-2/9 and oxidative stress in spontaneously hypertensive rats
title Fibulin-3 may improve vascular health through inhibition of MMP-2/9 and oxidative stress in spontaneously hypertensive rats
title_full Fibulin-3 may improve vascular health through inhibition of MMP-2/9 and oxidative stress in spontaneously hypertensive rats
title_fullStr Fibulin-3 may improve vascular health through inhibition of MMP-2/9 and oxidative stress in spontaneously hypertensive rats
title_full_unstemmed Fibulin-3 may improve vascular health through inhibition of MMP-2/9 and oxidative stress in spontaneously hypertensive rats
title_short Fibulin-3 may improve vascular health through inhibition of MMP-2/9 and oxidative stress in spontaneously hypertensive rats
title_sort fibulin-3 may improve vascular health through inhibition of mmp-2/9 and oxidative stress in spontaneously hypertensive rats
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4838143/
https://www.ncbi.nlm.nih.gov/pubmed/27035767
http://dx.doi.org/10.3892/mmr.2016.5036
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