The Circulating Level of FABP3 Is an Indirect Biomarker of MicroRNA-1

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

卷:61

Article

Varrone, Francesca¹  Gargano, Barbara¹  Carullo, Pierluigi^2,3  Di Silvestre, Dario⁴  De Palma, Antonella⁴  Grasso, Ludovica⁵  Di Somma, Carolina⁶  Mauri, Pierluigi⁴  Benazzi, Louise⁴  Franzone, Anna⁷  Jotti, Gloria Saccani⁸  Bang, Marie-Louise^2,3  Esposito, Giovanni⁷  Colao, Annamaria⁵  Condorelli, Gianluigi^2,3  Catalucci, Daniele^2,3 

[1] Multimed Hosp, IRCCS, Milan, Italy

[2] CNR, Biomed & Genet Res Inst, Milan Unit, I-20138 Milan, Italy

[3] Humanitas Clin & Res Ctr, Milan, Italy

[4] CNR, Inst Biomed Technol, I-20138 Milan, Italy

[5] Univ Naples Federico II, Sch Med, Endocrinol Sect, Dept Mol & Clin Endocrinol & Oncol, Naples, Italy

[6] SDN Fdn Naples, IRCCS, Naples, Italy

[7] Univ Naples Federico II, Dept Internal Med & Cardiovasc Sci, Naples, Italy

[8] Univ Parma, Dept Publ Hlth, I-43100 Parma, Italy

关键词: biomarker;    cardiovascular diseases;    FABP3;    microRNA;    miR-1;   

DOI  :  10.1016/j.jacc.2012.08.1003

来源: Elsevier

【 摘 要 】

Objectives This study sought to identify proteins from the cardiomyocyte (CM) secretome that are directly targeted by the muscle-specific microRNA-1 (miR-1), and thus reflect the pathophysiological state of the CM. Background MicroRNAs play critical regulatory roles during myocardial remodeling and progression to heart failure. However, it remains unknown whether secreted microRNA-targeted proteins can be used as indicators of myocardial microRNA expression and function. Methods A proteomic analysis based on multidimensional protein identification technology was performed on supernatants from cultured CMs overexpressing miR-1. Biochemical assays and an inducible cardiac-specific transgenic mouse model overexpressing miR-1 were used to demonstrate that heart-type fatty acid-binding protein-3 (FABP3) is a target of miR-1. Levels of miR-1 and FABP3 in cardiac tissue and plasma samples from mouse models as well as human patients were quantified by quantitative reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The study included wild-type mice subjected to ventricular pressure overload or fasting, as well as patients diagnosed with ventricular hypertrophy due to valvular aortic stenosis, acromegaly, or growth hormone deficiency, conditions associated with altered miR-1 expression. Results An inverse relationship between myocardial expression of miR-1 and circulating levels of FABP3 was found both in vitro and in vivo under various pathological conditions. Conclusions Assessment of FABP3 plasma levels in human patients might be used for indirectly measuring cardiac miR-1 activity. (J Am Coll Cardiol 2013;61:88-95) (C) 2013 by the American College of Cardiology Foundation

【 授权许可】

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