Investigation of Sudan IV staining areas in aortas of infants and children: possible prelesional stages of atherogenesis.
OBJECTIVE
Although atherosclerosis in infants and children is generally acknowledged, the temporal and spatial sequence of LDL insudation, modification and intimal monocyte accumulation has not been systematically studied. We have investigated herein very early stages of lesion formation in human aortas of individuals up to the age of 15 years. Aortic specimens from 61 cases (37 male, 24 female) were examined. 34 cases were <1 year old, 16 cases were between 1 and 5 years old, and 11 cases were between 6 and 15 years old. Areas preselected under a dissection microscope after Sudan IV staining were investigated in depth by immunohistochemical staining for apolipoprotein B, monocytes/macrophages, smooth muscle cells (SMCs), enzymatically and oxidatively modified lipoproteins, C-reactive protein and complement components.


RESULTS
(i) Lipoprotein accumulation in the intima before macrophage infiltration, (ii) virtually no extracellular lipoprotein modification, either enzymatic or oxidative, within intimal lesions in infancy (<1 year), (iii) onset of extracellular enzymatic modification of low-density lipoprotein (LDL) in the age group between 6 and 15 years and (iv) no coincidence of lipoprotein accumulation in the intima with activation of the terminal complement cascade as known from early atherosclerotic lesions in adults.


CONCLUSIONS
The present study indicates the existence of hitherto undescribed prelesional stages in atherogenesis characterized by 'inert' lipoprotein insudation in individuals <1 year of age without lipoprotein modification, monocyte/macrophage infiltration and/or inflammation on the one hand and the onset of extracellular enzymatic rather than oxidative lipoprotein modification in individuals between 6 and 15 years of age on the other hand. Further investigations of these stages should advance understanding of events underlying initiation, progression and regression of intimal lesions developing in early atherogenesis.
Torzewski
Michael
M
Institute of Clinical Chemistry and Laboratory Medicine, Johannes Gutenberg-University, Mainz, Germany. torzewski@zentrallabor.klinik.uni-mainz.de
Navarro
Bianca
B
Cheng
Fei
F
Canisius
Antje
A
Schmidt
Talkea
T
Bhakdi
Sucharit
S
Urban
Reinhard
R
Lackner
Karl J
KJ
D000293:Adolescent; D001011:Aorta / Q000378:metabolism / Q000473:pathology*; D001013:Aorta, Thoracic / Q000737:chemistry* / Q000378:metabolism; D001055:Apolipoproteins B / Q000378:metabolism; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology*; D001391:Azo Compounds; D002097:C-Reactive Protein / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008264:Macrophages / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000378:metabolism; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology
D001055:Apolipoproteins B; D001391:Azo Compounds; D002097:C-Reactive Protein; C009213:Scarlet Red