MicroRNA-210 Enhances Fibrous Cap Stability in Advanced Atherosclerotic Lesions

被引：115

作者：

Eken, Suzanne M. ^{[1
]}

Jin, Hong ^{[1
]}

Chernogubova, Ekaterina ^{[1
]}

Li, Yuhuang ^{[1
]}

Simon, Nancy ^{[1
]}

Sun, Changyan ^{[1
]}

Korzunowicz, Greg ^{[1
,2
]}

Busch, Albert ^{[1
]}

Backlund, Alexandra

Osterholm, Cecilia ^{[2
,3
]}

Razuvaev, Anton ^{[2
]}

Renne, Thomas ^{[2
,4
]}

Eckstein, Hans Henning ^{[5
,6
]}

Pelisek, Jaroslav ^{[5
,6
]}

Eriksson, Per ^{[1
]}

Diez, Maria Gonzlez ^{[1
]}

Matic, Ljubica Perisic ^{[2
]}

Schellinger, Isabel N. ^{[7
]}

Raaz, Uwe ^{[7
]}

Leeper, Nicholas J. ^{[8
]}

Hansson, Goran K. ^{[1
]}

Paulsson-Berne, Gabrielle ^{[1
]}

Hedin, Ulf ^{[2
]}

Maegdefessel, Lars ^{[1
,5
,6
]}

机构：

[1] Karolinska Inst, Dept Med, Stockholm, Sweden

[2] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden

[3] Nova Southeastern Univ, Cell Therapy Inst, Ft Lauderdale, FL USA

[4] Univ Med Ctr Hamburg Eppendorf, Inst Clin Chem & Lab Med, Hamburg, Germany

[5] Tech Univ Munich, Dept Vasc & Endovasc Surg, D-81765 Munich, Germany

[6] DZHK Partner Site Munich, Munich, Germany

[7] Georg August Univ Gottingen, Ctr Heart, Gottingen, Germany

[8] Stanford Univ, Div Cardiovasc Med, Palo Alto, CA 94304 USA

来源：

CIRCULATION RESEARCH | 2017年 / 120卷 / 04期

基金：

瑞典研究理事会; 欧洲研究理事会;

关键词：

adenomatous polyposis coli; atherosclerosis; carotid stenosis; microRNAs; stroke; SMOOTH-MUSCLE-CELLS; CAROTID-ENDARTERECTOMY; SHEAR-STRESS; PLAQUE; PROLIFERATION; ULTRASOUND; STENOSIS; MIR-210; HYPOXIA; CANCER;

D O I：

10.1161/CIRCRESAHA.116.309318

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Rationale: In the search for markers and modulators of vascular disease, microRNAs (miRNAs) have emerged as potent therapeutic targets. Objective: To investigate miRNAs of clinical interest in patients with unstable carotid stenosis at risk of stroke. Methods and Results: Using patient material from the BiKE (Biobank of Karolinska Endarterectomies), we profiled miRNA expression in patients with stable versus unstable carotid plaque. A polymerase chain reactionbased miRNA array of plasma, sampled at the carotid lesion site, identified 8 deregulated miRNAs (miR-15b, miR29c, miR-30c/d, miR-150, miR-191, miR-210, and miR-500). miR-210 was the most significantly downregulated miRNA in local plasma material. Laser capture microdissection and in situ hybridization revealed a distinct localization of miR-210 in fibrous caps. We confirmed that miR-210 directly targets the tumor suppressor gene APC (adenomatous polyposis coli), thereby affecting Wnt (Wingless-related integration site) signaling and regulating smooth muscle cell survival, as well as differentiation in advanced atherosclerotic lesions. Substantial changes in arterial miR-210 were detectable in 2 rodent models of vascular remodeling and plaque rupture. Modulating miR210 in vitro and in vivo improved fibrous cap stability with implications for vascular disease. Conclusions: An unstable carotid plaque at risk of stroke is characterized by low expression of miR-210. miR-210 contributes to stabilizing carotid plaques through inhibition of APC, ensuring smooth muscle cell survival. We present local delivery of miR-210 as a therapeutic approach for prevention of atherothrombotic vascular events.

引用

页码：633 / +

页数：36

共 47 条

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