An HMG-CoA Reductase Inhibitor, Cerivastatin, Suppresses Growth of Macrophages Expressing Matrix Metalloproteinases and Tissue Factor In Vivo and In Vitro

Aikawa, Masanori; Rabkin, Elena; Sugiyama, Seigo; Voglic, Sami J.; Fukumoto, Yoshihiro; Furukawa, Yutaka; Shiomi, Masashi; Schoen, Frederick J.; Libby, Peter

doi:10.1161/01.cir.103.2.276

Cited by 550 publications

(394 citation statements)

References 46 publications

(47 reference statements)

Supporting

Mentioning

355

Contrasting

Unclassified

Order By: Relevance

“…[53] Cerivastatin has been shown to decrease the levels of matrix metalloproteinase-1 (MMP-1), MMP-3, and MMP-9 in macrophages of Watanabe heritable hyperlipidemic rabbits. [54] In canine model of heart failure induced by microembolization dogs were treated with three months of rosuvastatin. Treatment with rosuvastatin resulted in the prevention of progressive LV dysfunction and remodeling and improvement in remodeling was similar to that seen after angiotensin converting enzyme inhibitor treatment.…”

Section: Ventricular Remodelingmentioning

confidence: 99%

Spectrum of Pleiotropic Effects of Statins in Heart Failure

Mathur

Ramasubbu

Mann

2008

Heart Failure Clinics

View full text Add to dashboard Cite

Section: Ventricular Remodelingmentioning

confidence: 99%

Spectrum of Pleiotropic Effects of Statins in Heart Failure

Mathur

Ramasubbu

Mann

2008

Heart Failure Clinics

View full text Add to dashboard Cite

“…Statins have also been shown to modify the function of ECs, smooth muscle cells, platelets, and monocytes/macrophages (22). Their effects include decreasing the expression of adhesion molecules in monocytes and leukocyte-endothelial interactions (23)(24)(25)(26), inhibiting platelet function (27), inhibiting tissue factor expression by mononuclear cells (28,29), down-regulating inflammatory cytokines in ECs (30), increasing fibrinolytic activity (31,32), and immunomodulation by decreasing the expression of class II major histocompatibility complex antigen (33).…”

Section: Conclusion These Findings Indicate That Fluvastatin Signifimentioning

confidence: 99%

Inhibition of the thrombogenic and inflammatory properties of antiphospholipid antibodies by fluvastatin in an in vivo animal model

Ferrara¹,

Liu²,

Espinola³

et al. 2003

Arthritis & Rheumatism

137

View full text Add to dashboard Cite

Methods. Two groups of CD-1 male mice, each comprising ϳ18 mice, were fed either normal saline solution or 15 mg/kg fluvastatin for 15 days. Each of the 2 groups was further subdivided to receive either purified IgG from patients with the antiphospholipid syndrome (IgG-APS) or normal IgG from healthy subjects. Analysis of thrombus dynamics was performed in treated and control mice, using a standardized thrombogenic injury procedure, and the area (size) of the thrombus was measured. Adhesion of leukocytes to ECs was analyzed with a microcirculation model of exposed cremaster muscle. Baseline and posttreatment soluble intercellular adhesion molecule 1 (sICAM-1) levels were determined by enzyme-linked immunosorbent assay.Results. IgG-APS mice treated with fluvastatin showed significantly smaller thrombi, a reduced number of adherent leukocytes, and decreased levels of sICAM-1 compared with IgG-APS animals treated with placebo.Conclusion. These findings indicate that fluvastatin significantly diminishes aPL-mediated thrombosis and EC activation in vivo. These results may have important implications for the design of new treatment strategies aimed at preventing recurrent thrombosis in patients with APS.

show abstract

“…Immunohistochemical study has shown that macrophages accumulated in the plaque express high levels of matrix metalloproteinases and tissue factors (9). These enzymes are considered to make the fibrous cap fragile (7-9) because they can digest the extracellular matrix in the fibrous cap and subsequently lead to thrombus formation (7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

“…These enzymes are considered to make the fibrous cap fragile (7-9) because they can digest the extracellular matrix in the fibrous cap and subsequently lead to thrombus formation (7)(8)(9). Based on such studies, rupture-prone plaques have come to be considered a crucial trigger in the process of sudden cardiac events and also a target for clinical intervention.…”

Section: Introductionmentioning

confidence: 99%

Correlation of Vulnerable Coronary Plaques to Sudden Cardiac Events. Lessons from a Myocardial Infarction-prone Animal Model (the WHHLMI Rabbit)

Shiomi

Ito

Yamada

et al. 2004

JAT

Self Cite

View full text Add to dashboard Cite

It is generally considered that coronary rupture-prone plaques play an important role in the onset of sudden cardiac events (acute coronary syndromes/sudden cardiac death). However, it is not clear which factors or stimuli are required to trigger plaque rupture and whether coronary plaques without occlusive thrombi can cause sudden cardiac events. To address these issues, recently, we developed a rabbit model of spontaneous myocardial infarction [ the Watanabe heritable hyperlipidemic (WHHL) MI rabbit ] and found that this model possessed several types of coronary plaques that are possibly correlated to sudden cardiac events. Although many of the coronary plaques of the WHHLMI rabbits appeared histologically to be rupture-prone in nature, true rupture was detected only in the few animals that died of MI. In addition, no occlusive thrombus was detected in any WHHLMI rabbit. These findings suggest that some additional stimuli play a definitive role in causing disruption of rupture-prone plaques and thrombosis. Nearly-occluded plaques caused by a luminal macrophage accumulation are the most common feature of WHHLMI rabbits, suggesting that they are responsible for sudden cardiac events. The WHHLMI rabbit could be a useful model for studying the mechanism(s) of plaque rupture and thrombogenesis if plaque rupture/thrombus formation is induced in the rupture-prone plaques of WHHLMI rabbits by administration of additional triggering factors, and could provide a novel means for developing new therapies.

show abstract

An HMG-CoA Reductase Inhibitor, Cerivastatin, Suppresses Growth of Macrophages Expressing Matrix Metalloproteinases and Tissue Factor In Vivo and In Vitro

Abstract: These results suggest that lipid lowering with HMG-CoA reductase inhibitors alters plaque biology by reducing proliferation and activation of macrophages, prominent sources of molecules responsible for plaque instability and thrombogenicity.

Cited by 550 publications

References 46 publications

Spectrum of Pleiotropic Effects of Statins in Heart Failure

Spectrum of Pleiotropic Effects of Statins in Heart Failure

Inhibition of the thrombogenic and inflammatory properties of antiphospholipid antibodies by fluvastatin in an in vivo animal model

Correlation of Vulnerable Coronary Plaques to Sudden Cardiac Events. Lessons from a Myocardial Infarction-prone Animal Model (the WHHLMI Rabbit)

Contact Info

Product

Resources

About