Author + information
- Hiroyasu Uzui,
- Hideki Hayashi,
- Izuru Nakae,
- Tetsuya Matsumoto,
- Hiroaki Uenishi,
- Hisae Hayasaki,
- Takayoshi Asaji,
- Shinobu Matsui,
- Kunihisa Miwa,
- Jong-Dae Lee,
- Tatsuya Sawamura and
- Masatoshi Fujita
Lectin-like oxidized LDL receptor 1 (LOX-1) system activation is involved in atherogenesis, however, molecular mechanisms of this system during plaque vulnerability remain elusive. We have previously reported that pericellularly localized membrane-type 1 matrix metalloproteinase (MT1-MMP) which is a main activator of secreted latent type MMPs, plays an important role in plaque vulnerability.
The aim of this study was to investigate the changes in the LOX-1 system and MT1-MMP expression in patients with hypercholesterolemia after the treatment of either pitavastatin or eicosapentaenoic acid (EPA). A total of 51 hypercholesterolemic patients who had not received anti-dyslipidemic agents and had LDL-C levels of more than 140 mg/dL were divided into two groups: group P received pitavastatin 2 mg once daily (n = 27), group E received EPA 1800 mg daily (n = 24). LOX-1 ligand, a soluble form of LOX-1 (sLOX-1) and MT1-MMP expression were measured before and at 6 months after treatment. Serum levels of LOX-1 with apolipoprotein B-100 particle ligand and sLOX-1 were measured by ELISA, expression of MT1-MMP on circulating peripheral blood mononuclear cells were examined for the frequencies of CD14 positive cells expressing MT1-MMP antigen at the single cell level using flow cytometry.
Low-density lipoprotein cholesterol (LDL-C) (162 ± 29 vs. 103 ± 29 mg/dL: p < 0.01), LOX-1 ligand (8.73 ± 3.30 vs. 5.51 ± 2.13 ng/mL: p < 0.01), and MT1-MMP expression (33.6 ± 3.1 vs. 30.3 ± 6.1%:p < 0.05) were significantly reduced in the group P, but there were no significant changes in high-density lipoprotein cholesterol (HDL-C) and sLOX-1. In the group E, there were no significant changes in LDL-C, LOX-1 ligand, MT1-MMP expression, HDL-C and sLOX-1, except the ratio of eicosapentaenoic acid to arachidonic acid (EPA/AA) (0.44 ± 0.21 vs. 1.19 ± 0.64 : p <0.01).
Pitavastatin therapy has beneficial effects on a marker of oxidative stress and pericellular MT1-MMP activity in hypercholesterolemic patients compared with EPA. These findings suggest that pitavastatin is useful in decreasing the plaque vulnerability in hypercholesterolemic patients.
Poster Sessions, Expo North
Monday, March 11, 2013, 9:45 a.m.-10:30 a.m.
Session Title: Prevention: Treatment of Hyperlipidemia
Abstract Category: 35. Vascular Medicine: Non Coronary Arterial Disease
Presentation Number: 1275-20
- 2013 American College of Cardiology Foundation