Journal Title
Title of Journal: J Nucl Cardiol
|
Abbravation: Journal of Nuclear Cardiology
|
Publisher
Springer-Verlag
|
|
|
|
Authors: Nezam Haider Dagmar Hartung Shinichiro Fujimoto Artiom Petrov Frank D Kolodgie Renu Virmani Satoru Ohshima Han Liu Jun Zhou Ai Fujimoto Atsuko Tahara Leo Hofstra Navneet Narula Chris Reutelingsperger Jagat Narula
Publish Date: 2009/08/07
Volume: 16, Issue: 5, Pages: 753-762
Abstract
Atherosclerosis was produced in rabbits receiving highcholesterol diet HC who underwent dual radionuclide imaging with 99mTclabeled matrix metalloproteinase inhibitor MPI and 111Inlabeled annexin A5 AA5 using microSPECT/CT ID/g MPI and AA5 uptake was measured followed by histological characterization Unmanipulated animals were used as disease controls Correlation between MPI and AA5 uptake was undertaken and relationship confirmed in culture study of activated THP1 monocytesMPI and AA5 uptake was best visualized in HC diet animals n = 6 and reduced significantly after fluvastatin treatment n = 4 or diet withdrawal n = 3 ID/g MPI 087 ± 018 and AA5 03 ± 01 uptake was higher in HC than control n = 6 animals 014 ± 004 P 0001 0007 ± 0002 P 0001 and reduced substantially after diet or statin intervention There was a significant correlation between MPI and AA5 uptake r = 62 P 0001 both correlated with pathologically verified MMP9 activity macrophage content and TUNEL staining In vitro studies demonstrated MMP9 release in culture medium from apoptotic THP1 monocytesIn twothirds of patients presenting with acute coronary syndromes coronary thrombosis is associated with rupture of the fibrous cap of an atherosclerotic plaque1 The triggers for the rupture include prevalence of monocytemacrophage infiltration and their apoptosis as well as cytokine production including matrix metalloproteinases MMP Almost one half of the macrophages at the site of plaque rupture demonstrate evidence of apoptosis with activation of caspase12 In vitro experiments have confirmed the role of caspase1 in induction of apoptosis and the use of caspase1 inhibitor YVAD substantially reduced the apoptosis of macrophages in an experimental model of atherosclerosis3 On the other hand macrophage infiltration in the plaque is associated with MMP expression and in turn to degradation of extracellular matrix and cap rupture4In addition to acting as a trigger to cap rupture macrophage apoptosis and MMP activity contribute to plaque vulnerability Apoptosis of macrophages in necrotic core5 leads to enlargement of the core size greater the necrotic core volume more prone is the plaque to rupture6 On the other hand the increase in MMP in the necrotic core promotes expansive outward remodeling of the plaque7 and renders the plaque susceptible to rupture These two processes which are independently critical for plaque rupture are both related to macrophage infiltration and it is logical to presume that these processes are interrelated The apoptosis of cellular components in an atherosclerotic plaque is no longer considered an inert process Fasinduced apoptosis of smooth muscle cell SMC has been shown to produce cytokines such as monocytechemoattractant protein 1 MCP1 CINC/IL8 and other proinflammatory genes resulting in an extensive macrophage infiltration8 Similar to the SMCrelated release of cytokines it is possible that apoptosis of macrophages may also be associated with secretory activity
Keywords:
.
|
Other Papers In This Journal:
|