Granulocyte macrophage colony-stimulating factor deficiency affects vascular elastin production and integrity of elastic lamellae.
BACKGROUND
Granulocyte macrophage colony-stimulating factor (GM-CSF) deficiency affects the production and fiber assembly/organization of the vascular collagenous matrix; structural alterations to the elastic system were observed. The present study elaborates the effect of GM-CSF deficiency on the vascular elastin system.


RESULTS
Histological examination of the aorta of GM-CSF-deficient mice revealed structurally altered elastic fibers. The elastic fiber area was significantly enhanced, whereas the remaining medial area was not affected. Aortic size was significantly increased. Reverse transcription polymerase chain reaction demonstrated decreased expression levels of tropoelastin, lysyl oxidase and bone morphogenetic protein 1 (BMP-1). Cell culture studies on vascular smooth muscle cells showed that after clearance of GM-CSF with GM-CSF antibodies, the tropoelastin mRNA expression was markedly reduced. Concomitantly, lysyl oxidase and BMP-1 mRNA levels were decreased. Treatment with GM-CSF stimulated the expression of these mRNAs.


CONCLUSIONS
Our studies demonstrate that disorganization of elastic lamellae as induced by GM-CSF deficiency is associated with adaptive vascular remodeling. The decreased tropoelastin expression observed is associated with elastic fiber hypertrophy. This paradox effect may be explained by decreased expression levels of lysyl oxidase and BMP-1, both mediating cross-linkage and thus assembly and organization of elastic fibers. From our data, we conclude that GM-CSF is a prerequisite for the maintenance of structural integrity of the vessel wall.
Weissen-Plenz
Gabriele
G
Leibniz Institute for Arteriosclerosis Research, Munster, Germany.
Eschert
Heike
H
Volker
Wolfgang
W
Sindermann
Jurgen R
JR
Beissert
Stefan
S
Robenek
Horst
H
Scheld
Hans H
HH
Breithardt
Gunter
G
D000818:Animals; D001011:Aorta / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D055395:Bone Morphogenetic Protein 1; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D004547:Elastic Tissue / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D004549:Elastin / Q000378:metabolism*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D008249:Protein-Lysine 6-Oxidase / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014333:Tropoelastin / Q000378:metabolism
D019485:Bone Morphogenetic Proteins; D012333:RNA, Messenger; D014333:Tropoelastin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D004549:Elastin; D008249:Protein-Lysine 6-Oxidase; D008666:Metalloendopeptidases; C525705:BMP1 protein, human; C525707:Bmp1 protein, mouse; D055395:Bone Morphogenetic Protein 1