Human macrophage foam cells degrade atherosclerotic plaques through cathepsin K mediated processes

BMC Cardiovascular Disorders

Research Article

Morten A Karsdal¹  Natasha Barascuk¹  Helene Skjøt-Arkil¹  Inger Byrjalsen¹  Claus Christiansen¹  Lise Larsen¹  Thomas C Register² 

[1] Nordic Bioscience A/S, DK-2730, Herlev, Denmark;Wake Forest University School of Medicine, Department of Pathology, Section on Comparative Medicine, Medical Center Boulevard, 27157, Winston-Salem, NC, USA;

关键词: Collagen Type;    Atherosclerotic Plaque;    Left Anterior Descend;    Atherosclerotic Lesion;    Foam Cell;   

DOI  :  10.1186/1471-2261-10-19

 received in 2009-08-28, accepted in 2010-04-21,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundProteolytic degradation of Type I Collagen by proteases may play an important role in remodeling of atherosclerotic plaques, contributing to increased risk of plaque rupture.The aim of the current study was to investigate whether human macrophage foam cells degrade the extracellular matrix (ECM) of atherosclerotic plaques by cathepsin K mediated processes.MethodsWe 1) cultured human macrophages on ECM and measured cathepsin K generated fragments of type I collagen (C-terminal fragments of Type I collagen (CTX-I) 2) investigated the presence of CTX-I in human coronary arteries and 3) finally investigated the clinical potential by measuring circulating CTX-I in women with and without radiographic evidence of aortic calcified atherosclerosis.ResultsImmune-histochemistry of early and advanced lesions of coronary arteries demonstrated co-localization of Cathepsin-K and CTX-I in areas of intimal hyperplasia and in shoulder regions of advanced plaques. Treatment of human monocytes with M-CSF or M-CSF+LDL generated macrophages and foam cells producing CTX-I when cultured on type I collagen enriched matrix. Circulating levels of CTX-I were not significantly different in women with aortic calcifications compared to those without.ConclusionsHuman macrophage foam cells degrade the atherosclerotic plaques though cathepsin K mediated processes, resulting in increase in levels of CTX-I. Serum CTX-I was not elevated in women with aortic calcification, likely due to the contribution of CTX-I from osteoclastic bone resorption which involves Cathepsin-K. The human macrophage model system may be used to identify important pathway leading to excessive proteolytic plaque remodeling and plaque rupture.

【 授权许可】

CC BY   
© Barascuk et al; licensee BioMed Central Ltd. 2010