Colocalization of oxidized low-density lipoprotein, caspase-3, cyclooxygenase-2, and macrophage migration inhibitory factor in arteriosclerotic human carotid arteries.
Apoptotic and inflammatory processes occur in human arteriosclerotic lesions. We examined the hypothesis whether both processes are possibly associated by studying the colocalization of corresponding markers. In 11 human arteriosclerotic carotid arteries, proapoptotic markers (CPP32 (caspase-3), poly(ADP-ribose) polymerase, apoptosis-inducing factor, c-Jun/AP-1, and p53) and proinflammatory markers (macrophage migration inhibitory factor (MIF) and cyclooxygenase-2) were found in macrophages (MPhi) evaluated by computer-assisted immunohistomorphometry. Double-labeling studies demonstrated a colocalization of, both, proapoptotic and proinflammatory markers in these MPhi. Moreover, these MPhi also contained oxidized low-density lipoproteins (oxLDL). Exposure of cultured human MPhi to oxLDL, C6-ceramide, and tumor necrosis factor-alpha or H2O2 resulted in a significant increase of the apoptosis rate as well as of the MIF protein expression. Our study of MPhi in arteriosclerotic carotid arteries and in vitro experiments provide evidence that markers of apoptosis and inflammation are not only significantly increased but are also coexpressed. We conclude there are reciprocal modulatory interactions between apoptotic and inflammatory pathways in human plaque MPhi, which might importantly modify plaque progression or stability.
Schlittenhardt
Daniel
D
Department of Anatomy & Cell Biology III and Interdisciplinary Center of Neurosciences, University of Heidelberg, Im Neuenheimer Feld 307, 69120, Heidelberg, Germany.
Schmiedt
Walther
W
Bonaterra
Gabriel A
GA
Metz
Jürgen
J
Kinscherf
Ralf
R
D017209:Apoptosis / Q000502:physiology; D001161:Arteriosclerosis / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D002340:Carotid Artery Diseases / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002478:Cells, Cultured; D002518:Ceramides / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007150:Immunohistochemistry; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000494:pharmacology; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D002518:Ceramides; D008077:Lipoproteins, LDL; D008263:Macrophage Migration-Inhibitory Factors; D014409:Tumor Necrosis Factor-alpha; C101954:N-caproylsphingosine; D006861:Hydrogen Peroxide; D051546:Cyclooxygenase 2; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases