Warning: Undefined variable $zfal in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 525
Deprecated: str_replace(): Passing null to parameter #3 ($subject) of type array|string is deprecated in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 525
Warning: Undefined variable $sterm in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 530
 free
Warning: Undefined variable $sterm in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 531
 free
 free
 
English Wikipedia
Nephropedia Template TP (
Twit Text
DeepDyve
Pubget Overpricing |  
lüll
Signal transducer and activator of transcription-1 is critical for apoptosis in macrophages subjected to endoplasmic reticulum stress in vitro and in advanced atherosclerotic lesions in vivo Lim WS; Timmins JM; Seimon TA; Sadler A; Kolodgie FD; Virmani R; Tabas ICirculation 2008[Feb]; 117 (7): 940-51BACKGROUND: Macrophage apoptosis is a critical process in the formation of necrotic cores in vulnerable atherosclerotic plaques. In vitro and in vivo data suggest that macrophage apoptosis in advanced atheromata may be triggered by a combination of endoplasmic reticulum stress and engagement of the type A scavenger receptor, which together induce death through a rise in cytosolic calcium and activation of toll-like receptor-4. METHODS AND RESULTS: Using both primary peritoneal macrophages and studies in advanced atheromata in vivo, we introduce signal transducer and activator of transcription-1 (STAT1) as a critical and necessary component of endoplasmic reticulum stress/type A scavenger receptor-induced macrophage apoptosis. We show that STAT1 is serine phosphorylated in macrophages subjected to type A scavenger receptor ligands and endoplasmic reticulum stress in a manner requiring cytosolic calcium, calcium/calmodulin-dependent protein kinase II, and toll-like receptor-4. Remarkably, apoptosis was inhibited by approximately 80% to 90% (P<0.05) by STAT1 deficiency or calcium/calmodulin-dependent protein kinase II inhibition. In vivo, nuclear Ser-P-STAT1 was found in macrophage-rich regions of advanced murine and human atheromata. Most important, macrophage apoptosis was decreased by 61% (P=0.034) and plaque necrosis by 34% (P=0.02) in the plaques of fat-fed low density lipoprotein receptor null Ldlr-/- mice transplanted with Stat1-/- bone marrow. CONCLUSIONS: STAT1 is critical for endoplasmic reticulum stress/type A scavenger receptor-induced apoptosis in primary tissue macrophages and in macrophage apoptosis in advanced atheromata. These findings suggest a potentially important role for STAT1-mediated macrophage apoptosis in atherosclerotic plaque progression.|Animals[MESH]|Apoptosis/*physiology[MESH]|Atherosclerosis/metabolism/*pathology[MESH]|Bone Marrow Transplantation[MESH]|Calcium Signaling[MESH]|Calcium-Calmodulin-Dependent Protein Kinase Type 2/physiology[MESH]|Endoplasmic Reticulum/*physiology[MESH]|Female[MESH]|Humans[MESH]|In Situ Nick-End Labeling[MESH]|Macrophages, Peritoneal/metabolism/*pathology[MESH]|Mice[MESH]|Mice, Inbred C57BL[MESH]|Mice, Knockout[MESH]|Phosphorylation[MESH]|Phosphoserine/metabolism[MESH]|Protein Processing, Post-Translational[MESH]|Radiation Chimera[MESH]|Receptors, LDL/deficiency/genetics[MESH]|STAT1 Transcription Factor/analysis/deficiency/genetics/*physiology[MESH]|Scavenger Receptors, Class A/drug effects/physiology[MESH]|Toll-Like Receptor 4/physiology[MESH] |
