on February 15, 2007
Published online before print February 15, 2007, doi: 10.1161/ATVBAHA.106.134080
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Submitted on June 16, 2006
Accepted on January 26, 2007
Early Human Atherosclerosis. Accumulation of Lipid and Proteoglycans in Intimal Thickenings Followed by Macrophage Infiltration
Yutaka Nakashima *;
From Pathophysiological and Experimental Pathology (Y.N., H.F., S.S., K.S.), Graduate School of Medical Sciences, Kyushu University, Japan; the Division of Pathology (Y.N.), Fukuoka Red Cross Hospital, Fukuoka, Japan; and the Hope Heart Program at The Benaroya Research Institute and the University of Washington (T.N.W.), Seattle.
* To whom correspondence should be addressed. E-mail: y-nakashima{at}fukuoka-med.jrc.or.jp.
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.
Methods and 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.
Key words: early human atherosclerosis • diffuse intimal thickening • fatty streak • lipid retention • biglycan
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