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Int. J. Mol. Sci. 2015, 16(12), 28800-28811; doi:10.3390/ijms161226131

Possible Mechanisms of Di(2-ethylhexyl) Phthalate-Induced MMP-2 and MMP-9 Expression in A7r5 Rat Vascular Smooth Muscle Cells

1
Department of Pharmacy, Chia-Nan University of Pharmacy and Science, Tainan 717, Taiwan
2
Department of Biochemistry and Chemistry, National Chung Cheng University, Chia-Yi 621, Taiwan
*
Author to whom correspondence should be addressed.
Academic Editor: Baohong Zhang
Received: 20 August 2015 / Revised: 17 November 2015 / Accepted: 18 November 2015 / Published: 4 December 2015
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Abstract

Proliferation and migration of vascular smooth muscle cells (VSMC) are important in the development and/or progression of many cardiovascular diseases, including atherosclerosis. Evidence shows that matrix metalloproteinase (MMP)-2 and MMP-9 are related to the pathogenesis of atherosclerosis. The expressions of MMP-2 and MMP-9 in atherosclerosis are regulated via various pathways, such as p38 mitogen activated protein kinase (MAPK), extracellular signal regulated kinase 1 and 2 (ERK1/2), Akt, and nuclear factor kappa (NF-κB). Di(2-ethylhexyl) phthalate (DEHP) has been shown to induce atherosclerosis by increasing tumor necrosis factor (TNF)-α, interleukin (IL)-6, and intercellular adhesion molecule (ICAM) productions. However, whether DEHP poses any effects on MMP-2 or MMP-9 expression in VSMC has not yet been answered. In our studies, rat aorta VSMC was treated with DEHP (between 2 and 17.5 ppm) and p38 MAPK, ERK1/2, Akt, NF-κB, and MMP-2 and MMP-9 proteins and activities were measured. Results showed that the presence of DEHP can induce higher MMP-2 and MMP-9 expression than the controls. Similar results on MMP-regulating proteins, i.e., p38 MAPK, ERK1/2, Akt, and NF-κB, were also observed. In summary, our current results have showed that DEHP can be a potent inducer of atherosclerosis by increasing MMP-2 and MMP-9 expression at least through the regulations of p38 MAPK, ERK1/2, Akt, and NF-κB. View Full-Text
Keywords: di(2-ethylhexyl) phthalate (DEHP); vascular smooth muscle cells (VSMC); MMP-2; MMP-9; p38 MAPK; ERK1/2; Akt; NF-κB di(2-ethylhexyl) phthalate (DEHP); vascular smooth muscle cells (VSMC); MMP-2; MMP-9; p38 MAPK; ERK1/2; Akt; NF-κB
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Shih, M.-F.; Pan, K.-H.; Cherng, J.Y. Possible Mechanisms of Di(2-ethylhexyl) Phthalate-Induced MMP-2 and MMP-9 Expression in A7r5 Rat Vascular Smooth Muscle Cells. Int. J. Mol. Sci. 2015, 16, 28800-28811.

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