Cardiovascular Research Advance Access first published online on April 22, 2008
This version [Corrected Proof] published online on May 12, 2008
Cardiovascular Research, doi:10.1093/cvr/cvn099
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Early atherosclerosis in humans: role of diffuse intimal thickening and extracellular matrix proteoglycans
1 Division of Pathology, Fukuoka Red Cross Hospital, 3-1-1 Ogusu, Minami-ku, Fukuoka 815-8555, Japan
2 The Hope Heart Program, Benaroya Research Institute, 1201 Ninth Ave., Seattle, WA 98101, USA
3 University of Washington, Seattle, WA 98195, USA
4 Pathophysiological and Experimental Pathology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
* Corresponding author. Tel: +81 92 521 1211; fax: +81 92 533 9960. E-mail address: y-nakashima{at}fukuoka-med.jrc.or.jp
This review attempts to define the early events that lead to lesions of human atherosclerosis based on careful morphological studies in human autopsy specimens. In contrast to most small laboratory animals, diffuse intimal thickening (DIT) is present in human arteries before atherosclerosis develops, particularly in the atherosclerosis-prone arteries such as coronary arteries and abdominal aorta. In the earliest stage of atherosclerosis, lipids deposit eccentrically in the deep layer of DIT to form Type I lesions. These layers are enriched in extracellular matrix (ECM) proteoglycans such as biglycan. Following lipid deposition, macrophages appear in these regions and foam cells are observed (Type II lesions). Such observations support the ‘response-to-retention’ hypothesis that states that a principle early event in the pathogenesis of human atherosclerosis is the trapping and retention of lipoproteins by ECM proteoglycans followed by infiltration and accumulation of macrophages.
KEYWORDS Arteries; Human; Extracellular matrix; Early atherosclerosis; Proteoglycans; Lipoproteins
Time for primary review: 34 days