Fibulin-3 may improve vascular health through inhibition of MMP-2/9 and oxidative stress in spontaneously hypertensive rats.
Fibulin-3 may improve vascular health through inhibition of MMP-2/9 and oxidative stress in spontaneously hypertensive rats.
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Fibulin-3 可能通过抑制自发性高血压大鼠的 MMP-2/9 和氧化应激来改善血管健康。
DOI：
10.3892/mmr.2016.5036
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发表时间：
2016-05
影响因子：
3.4
通讯作者：
Xiang D
中科院分区：
文献类型：
--
作者：
Lin Z;Wang Z;Li G;Li B;Xie W;Xiang D
纤维蛋白-3已被认为在细胞外基质的重塑中起作用，但其在高血压血管重塑中的作用尚不清楚。本研究采用Wistar-Kyoto （WKY）大鼠10只（对照组）和自发性高血压大鼠30只（SHRs）。SHRs随机分为三组：安慰剂组，静脉注射生理盐水；FBLN-1组，低剂量纤维蛋白-3蛋白（静脉注射，120 ng/kg）；FBLN-2组给予高剂量纤维蛋白-3蛋白（静脉注射；240 ng/kg）。组织学分析分析血管重构。采用免疫组化、western blotting和逆转录-定量聚合酶链反应检测大鼠组织中纤维蛋白-3、基质金属蛋白酶(MMP)-2、MMP-9和组织金属蛋白酶抑制剂(TIMP)-3的表达。氧化应激检测采用双氢乙胺染色法。SHRs的收缩压（SBP）显著高于WKY大鼠（P<0.05）。与安慰剂组相比，FBLN-2组的收缩压显著降低（182±12 mmHg vs 224±14 mmHg； P<0.05）。SHR组（安慰剂组、FBLN-1组、FBLN-2组）胸主动脉壁厚度均显著厚于对照组（P<0.01）。FBLN-2组的壁厚显著大于安慰剂组和FBLN-1组（124.2±11.8 μm vs. 106.9±9.5 μm和96.8±10.2 μm； P<0.05）。安慰剂组、FBLN-1组和FBLN-2组的壁腔比均显著大于对照组（P<0.05）。此外，与对照组相比，安慰剂组胸主动脉纤维蛋白-3和MMP-2/9蛋白和mRNA水平的表达水平均显著升高（P<0.05）。与安慰剂组相比，FBLN-2组MMP-2/9水平显著降低（P<0.05）。而四组间TIMP-3水平差异无统计学意义（P < 0.05）。与对照组相比，安慰剂组的活性氧（ROS）增加。Fibulin-3能够减轻FBLN组的ROS水平。这表明纤维蛋白-3可能在动脉中起生长因子的作用。此外，结果表明，纤维蛋白-3可能降低高血压血管重构中MMP-2和-9的水平以及氧化应激。上调纤维蛋白-3可能有利于改善血管健康和抵消高血压的某些心血管危险因素。
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.