title: Possible Mechanisms of Di(2-ethylhexyl) Phthalate-Induced MMP-2 and MMP-9 Expression in A7r5 Rat Vascular Smooth Muscle Cells.
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.
authors.affiliation: Department of Pharmacy, Chia-Nan University of Pharmacy and Science, Tainan 717, Taiwan. meifenshih@mail.cnu.edu.tw.
authors.forename: Mei-Fen
authors.initials: MF
authors.lastname: Shih
authors.affiliation: Department of Biochemistry and Chemistry, National Chung Cheng University, Chia-Yi 621, Taiwan. s9923042@gmail.com.
authors.forename: Kuang-Hung
authors.initials: KH
authors.lastname: Pan
authors.affiliation: Department of Biochemistry and Chemistry, National Chung Cheng University, Chia-Yi 621, Taiwan. chejyc@ccu.edu.tw.
authors.forename: Jong Yuh
authors.initials: JY
authors.lastname: Cherng
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000139:chemically induced / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004051:Diethylhexyl Phthalate / Q000009:adverse effects*; D052244:Endocrine Disruptors / Q000009:adverse effects*; D004785:Environmental Pollutants / Q000009:adverse effects*; D020778:Matrix Metalloproteinase 2 / Q000032:analysis / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000032:analysis / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000032:analysis / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000032:analysis / Q000378:metabolism; D010968:Plasticizers / Q000009:adverse effects; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000032:analysis / Q000378:metabolism
chemical_list: D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D016328:NF-kappa B; D010968:Plasticizers; D004051:Diethylhexyl Phthalate; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: Akt; ERK1/2; MMP-2; MMP-9; NF-κB; di(2-ethylhexyl) phthalate (DEHP); p38 MAPK; vascular smooth muscle cells (VSMC)