Deep sea water prevents balloon angioplasty-induced hyperplasia through MMP-2: an in vitro and in vivo study.
Major facts about the development of restenosis include vascular smooth muscle cells (VSMCs) proliferation and migration. A previous study showed that in vitro treatment with magnesium chloride has the potential to affect the proliferation and migration of VSMCs. Magnesium is the major element in deep sea water (DSW) and is a biologically active mineral. It is unclear whether DSW intake can prevent abnormal proliferation and migration of VSMCs as well as balloon angioplasty-induced neointimal hyperplasia. Thus, we attempted to evaluate the anti-restenotic effects of DSW and its possible molecular mechanisms. Several concentrations of DSW, based on the dietary recommendations (RDA) for magnesium, were applied to a model of balloon angioplasty in SD rats. The results showed that DSW intake markedly increased magnesium content within the vascular wall and reduced the development of neointimal hyperplasia. The immunohistochemical analysis also showed that the expression of proteins associated with cell proliferation and migration were decreased in the balloon angioplasty groups with DSW supplement. Furthermore, in vitro treatment with DSW has a dose-dependent inhibitory effect on serum-stimulated proliferation and migration of VSMCs, whose effects might be mediated by modulation of mitogen-activated protein kinase (MAPK) signaling and of the activity of matrix metalloproteinase-2 (MMP-2). Our study suggested that DSW intake can help prevent neointimal hyperplasia (or restenosis), whose effects may be partially regulated by magnesium and other minerals.
School of Pharmacy, China Medical University, Taichung, Taiwan.
Pei-Chuan
PC
Li
College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
Chun-Hsu
CH
Pan
School of Pharmacy, China Medical University, Taichung, Taiwan.
Ming-Jyh
MJ
Sheu
Department of Public Health, China Medical University, Taichung, Taiwan.
Chin-Ching
CC
Wu
School of Nursing, China Medical University, Taichung, Taiwan.
Wei-Fen
WF
Ma
School of Pharmacy, China Medical University, Taichung, Taiwan; College of Pharmacy, Taipei Medical University, Taipei, Taiwan; Department of Biological Science and Technology, China Medical University, Taichung, Taiwan.
Chieh-Hsi
CH
Wu
D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D006965:Hyperplasia / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012623:Seawater
D020778:Matrix Metalloproteinase 2