MicroRNA-210 Enhances Fibrous Cap Stability in Advanced Atherosclerotic Lesions. Issue 4 (17th February 2017)

• Record Type: Journal Article
• Authors: Eken, Suzanne M.; Jin, Hong; Chernogubova, Ekaterina; Li, Yuhuang; Simon, Nancy; Sun, Changyan; Korzunowicz, Greg; Busch, Albert; Bäcklund, Alexandra; Österholm, Cecilia; Razuvaev, Anton; Renné, Thomas; Eckstein, Hans Henning; Pelisek, Jaroslav; Eriksson, Per; González Díez, María; Perisic Matic, Ljubica; Schellinger, Isabel N.; Raaz, Uwe; Leeper, Nicholas J.; Hansson, Göran K.; Paulsson-Berne, Gabrielle; Hedin, Ulf; Maegdefessel, Lars
• Is Part Of: Circulation research. Volume 120:Issue 4(2017)
• Publication Date: 2017-02-17
• Subjects: adenomatous polyposis coli -- atherosclerosis -- carotid stenosis -- microRNAs -- stroke; Cardiovascular system -- Periodicals; Blood -- Circulation -- Periodicals; Blood Circulation; Cardiovascular System; Vascular Diseases; Sang -- Circulation -- Périodiques; Appareil cardiovasculaire -- Périodiques; 612.1
• DOI: 10.1161/CIRCRESAHA.116.309318
• Languages: English
• ISSNs: 0009-7330

Abstract

Abstract : 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 reaction–based miRNA array of plasma, sampled at the carotid lesion site, identified 8 deregulated miRNAs (miR-15b, miR-29c, 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 miR-210 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. Abstract : Supplemental Digital Content is available in the text.