Macrophage-Derived Matrix Vesicles: An Alternative Novel Mechanism for Microcalcification in Atherosclerotic Plaques

被引：364

作者：

New, Sophie E. P. ^{[1
]}

Goettsch, Claudia ^{[1
]}

Aikawa, Masanori ^{[1
,2
,3
]}

Marchini, Julio F. ^{[2
,3
]}

Shibasaki, Manabu ^{[1
]}

Yabusaki, Katsumi ^{[1
]}

Libby, Peter ^{[2
,3
]}

Shanahan, Catherine M. ^{[4
]}

Croce, Kevin

Aikawa, Elena ^{[1
,2
,3
]}

机构：

[1] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Interdisciplinary Cardiovasc Sci, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Excellence Vasc Biol, Boston, MA 02115 USA

[4] Kings Coll London, Div Cardiovasc, London WC2R 2LS, England

来源：

CIRCULATION RESEARCH | 2013年 / 113卷 / 01期

基金：

美国国家卫生研究院;

关键词：

atherosclerosis; calcification; extracellular vesicles; inflammation; macrophages; renal insufficiency; chronic; rupture; AORTIC-VALVE CALCIFICATION; ANNEXIN A6; ARTERIAL; MINERALIZATION; DISEASE;

D O I：

10.1161/CIRCRESAHA.113.301036

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Rationale: We previously showed that early calcification of atherosclerotic plaques associates with macrophage accumulation. Chronic renal disease and mineral imbalance accelerate calcification and the subsequent release of matrix vesicles (MVs), precursors of microcalcification. Objective: We tested the hypothesis that macrophage-derived MVs contribute directly to microcalcification. Methods and Results: Macrophages associated with regions of calcified vesicular structures in human carotid plaques (n=136 patients). In vitro, macrophages released MVs with high calcification and aggregation potential. MVs expressed exosomal markers (CD9 and TSG101) and contained S100A9 and annexin V. Silencing S100A9 in vitro and genetic deficiency in S100A9(-/-) mice reduced MV calcification, whereas stimulation with S100A9 increased calcification potential. Externalization of phosphatidylserine after Ca/P stimulation and interaction of S100A9 and annexin V indicated that a phosphatidylserine-annexin V-S100A9 membrane complex facilitates hydroxyapatite nucleation within the macrophage-derived MV membrane. Conclusions: Our results support the novel concept that macrophages release calcifying MVs enriched in S100A9 and annexin V, which contribute to accelerated microcalcification in chronic renal disease.

引用

页码：72 / 77

页数：6

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