Early human atherosclerosis: accumulation of lipid and proteoglycans in intimal thickenings followed by macrophage infiltration.
OBJECTIVE
The present study was designed to clarify the morphological features of early human atherosclerosis and to determine whether specific extracellular matrix proteoglycans play a role in early atherogenesis.


RESULTS
Step and serial sections were obtained from right coronary arteries with no or early atherosclerosis. Atherosclerosis was classified into 4 grades according to the amount of lipid deposition. Coronary arteries with Grade 0 showed diffuse intimal thickening (DIT) with no lipid deposits. The extracellular matrix proteoglycans, biglycan and decorin, were localized in the outer layer of DIT. Most cases of Grade 1 and Grade 2 exhibited fatty streaks with extracellular lipids colocalizing with biglycan and decorin in the outer layer of the intima. As lipid grades increased, macrophages increased in number and were present in the deeper layers. Most cases of Grade 3 exhibited pathologic intimal thickening (PIT) with extracellular lipids underneath a layer of foam cell macrophages.


CONCLUSIONS
In early human coronary atherosclerosis, fatty streaks develop via extracellular deposition of lipids associated with specific types of proteoglycans in the outer layer of preexisting DIT. As the amount of the lipid increases in fatty streaks, macrophages infiltrate toward the deposited lipid to form PIT with foam cells.
Nakashima
Yutaka
Y
Graduate School of Medical Sciences, Kyushu University, Japan. y-nakashima@fukuoka-med.jrc.or.jp
Fujii
Hiroshi
H
Sumiyoshi
Shinji
S
Wight
Thomas N
TN
Sueishi
Katsuo
K
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D050197:Atherosclerosis / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D002102:Cadaver; D002452:Cell Count; D018932:Chemokine CCL2 / Q000378:metabolism; D002648:Child; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D021621:Imaging, Three-Dimensional; D050356:Lipid Metabolism / Q000502:physiology*; D008074:Lipoproteins / Q000378:metabolism*; D008264:Macrophages / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011509:Proteoglycans / Q000378:metabolism*; D012720:Severity of Illness Index; D017539:Tunica Intima / Q000378:metabolism* / Q000473:pathology
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D008074:Lipoproteins; D011509:Proteoglycans