MMP-9 inhibition by ACE inhibitor reduces oxidized LDL-mediated foam-cell formation.

نویسندگان

  • Chiari Kojima
  • Jun Ino
  • Hideto Ishii
  • Kosaku Nitta
  • Masayuki Yoshida
چکیده

AIM Angiotensin-converting enzyme inhibitors (ACEIs) have been shown to block matrix metalloproteinase (MMP)-9 activity, which plays a role in atherogenesis. MMP-9 activity of macrophages is increased during foam cell formation. To investigate the contribution of ACEIs to foam cell formation, we studied the effects of an ACEI, imidaprilat, on THP-1 macrophages and the underlying molecular mechanisms in vitro. 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.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Compare the Effect of Eicosapentaenoic Acid and Oxidized Low-Density Lipoprotein on the Expression of CD36 and Peroxisome Proliferator-Activated Receptor Gamma

Background: There is evidence that CD36 promotes foam cell formation through internalizing oxidized LDL (ox-LDL) into macrophages therefore, it plays a key role in pathogenesis of atherosclerosis. In addition, CD36 expression seems to be mediated by nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-γ). The aim of the present study was to evaluate and compare the effect of ...

متن کامل

Pomegranate juice inhibits oxidized LDL uptake and cholesterol biosynthesis in macrophages.

Macrophage cholesterol accumulation and foam cell formation are the hallmarks of early atherogenesis. Pomegranate juice (PJ) was shown to inhibit macrophage foam cell formation and development of atherosclerotic lesions. The aim of this study was to elucidate possible mechanisms by which PJ reduces cholesterol accumulation in macrophages. J774.A1 macrophages were preincubated with PJ followed b...

متن کامل

Inhibitory effect of Cinnamon on prevention of foam cell formation in platelet and monocytes co-culture

Introduction: Atherosclerosis is one of the leading causes of cardiovascular disease. Following endothelial damage and platelet aggregation in that area and the recruitment of monocytes and their conversion to macrophages, LDL gradually accumulates under the endothelial artery wall and gradually oxidized and convert to oxi-LDL. By swallowing it, the macrophages turn into foam cell and then athe...

متن کامل

Recombinant Human Thioredoxin-1 Protects Macrophages from Oxidized Low-Density Lipoprotein-Induced Foam Cell Formation and Cell Apoptosis

Oxidized low-density lipoprotein (ox-LDL)-induced macrophage foam cell formation and apoptosis play critical roles in the pathogenesis of atherosclerosis. Thioredoxin-1 (Trx) is an antioxidant that potently protects various cells from oxidative stress-induced cell death. However, the protective effect of Trx on ox-LDL-induced macrophage foam cell formation and apoptosis has not been studied. Th...

متن کامل

Angiotensin II induces LOX-1, the human endothelial receptor for oxidized low-density lipoprotein.

BACKGROUND Oxidatively modified LDL (oxLDL) plays an important role in the development of atherosclerosis. OxLDL effects, eg, foam cell formation, are mediated in part by the classic scavenger receptor, whereas other effects may involve the recently cloned endothelial oxLDL receptor, LOX-1 (lectinlike oxLDL receptor-1), which is distinct from macrophage scavenger receptors. Because the regulati...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Journal of atherosclerosis and thrombosis

دوره 17 1  شماره 

صفحات  -

تاریخ انتشار 2010