Published online before print February 15, 2007, doi: 10.1161/ATVBAHA.106.134080
© 2007 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Early Human Atherosclerosis
Accumulation of Lipid and Proteoglycans in Intimal Thickenings Followed by Macrophage Infiltration
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.
Correspondence to Yutaka Nakashima, MD, PhD, Division of Pathology, Fukuoka Red Cross Hospital, 3-1-1 Ogusu, Minami-ku, Fukuoka 815-8555, Japan. 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.
Little is known how early human atherosclerosis evolves. Our results showed that fatty streaks develop via extracellular lipid deposition in the proteoglycan-enriched outer layer of preexisting diffuse intimal thickening. As the amount of lipid increases, macrophages infiltrate toward the deposited lipid to form pathologic intimal thickening with foam cells.
Key Words: early human atherosclerosis • diffuse intimal thickening • fatty streak • lipid retention • biglycan
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