Abstract | AIM: METHODS AND RESULTS: Pre-treatment of THP-1 macrophages with imidaprilat (100 nmol/L, 4 hours) significantly decreased foam cell formation induced by oxidized LDL ( OxLDL). Imidaprilat reduced the protein level of MMP-9 in THP-1 macrophages and attenuated OxLDL-induced MMP-9 activity in the culture supernatants. Indeed, pretreatment of THP-1 macrophages with an MMP-2/9 inhibitor (20 micromol/L, 4 hours) attenuated OxLDL-induced foam-cell formation. Imidaprilat or the MMP-2/9 inhibitor blocked OxLDL-induced expressions of LOX-1 and scavenger receptor-A (SR-A), but not that of CD36, in THP-1 macrophages. In addition, OxLDL-induced activation of p38 mitogen-activated protein kinase (MAPK) and ERK, but not JNK, was blunted by imidaprilat or the MMP-2/9 inhibitor. Finally, siRNA against MMP-9 inhibited foam cell formation as well as lipid accumulation in THP-1 macrophages. CONCLUSION: These findings suggest that imidaprilat reduces OxLDL-triggered foam-cell formation in THP-1 macrophages via modulation of MMP-9 activity and may indicate a novel antiinflamma-tory mechanism of imidaprilat in atherogenesis.
|
Authors | Chiari Kojima, Jun Ino, Hideto Ishii, Kosaku Nitta, Masayuki Yoshida |
Journal | Journal of atherosclerosis and thrombosis
(J Atheroscler Thromb)
Vol. 17
Issue 1
Pg. 97-105
(Feb 2010)
ISSN: 1880-3873 [Electronic] Japan |
PMID | 20093780
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Angiotensin-Converting Enzyme Inhibitors
- Imidazolidines
- Lipoproteins, LDL
- Matrix Metalloproteinase Inhibitors
- OLR1 protein, human
- RNA, Small Interfering
- Scavenger Receptors, Class A
- Scavenger Receptors, Class E
- oxidized low density lipoprotein
- Mitogen-Activated Protein Kinases
- Matrix Metalloproteinase 2
- Matrix Metalloproteinase 9
- imidaprilat
|
Topics |
- Angiotensin-Converting Enzyme Inhibitors
(pharmacology)
- Cell Line
- Enzyme Activation
(drug effects)
- Foam Cells
(cytology, drug effects, metabolism)
- Humans
- Imidazolidines
(pharmacology)
- Lipoproteins, LDL
(metabolism)
- Matrix Metalloproteinase 2
(metabolism)
- Matrix Metalloproteinase 9
(genetics, metabolism)
- Matrix Metalloproteinase Inhibitors
- Mitogen-Activated Protein Kinases
(metabolism)
- Monocytes
(cytology, drug effects, metabolism)
- RNA, Small Interfering
- Scavenger Receptors, Class A
(metabolism)
- Scavenger Receptors, Class E
(metabolism)
|