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Mol Med Rep. 2016 May;13(5):3805-12. doi: 10.3892/mmr.2016.5036. Epub 2016 Mar 21.

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

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Department of Cardiology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, Guangdong 510000, P.R. China.
Department of Pathology, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
Department of Cardiology, Guangzhou General Hospital of Guangzhou Military Command, Southern Medical University, Guangzhou, Guangdong 510110, P.R. China.


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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