title: miR-222 is necessary for exercise-induced cardiac growth and protects against pathological cardiac remodeling.
abstract: Exercise induces physiological cardiac growth and protects the heart against pathological remodeling. Recent work suggests exercise also enhances the heart's capacity for repair, which could be important for regenerative therapies. While microRNAs are important in certain cardiac pathologies, less is known about their functional roles in exercise-induced cardiac phenotypes. We profiled cardiac microRNA expression in two distinct models of exercise and found microRNA-222 (miR-222) was upregulated in both. Downstream miR-222 targets modulating cardiomyocyte phenotypes were identified, including HIPK1 and HMBOX1. Inhibition of miR-222 in vivo completely blocked cardiac and cardiomyocyte growth in response to exercise while reducing markers of cardiomyocyte proliferation. Importantly, mice with inducible cardiomyocyte miR-222 expression were resistant to adverse cardiac remodeling and dysfunction after ischemic injury. These studies implicate miR-222 as necessary for exercise-induced cardiomyocyte growth and proliferation in the adult mammalian heart and show that it is sufficient to protect the heart against adverse remodeling.
authors: Cardiovascular Division of the Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
authors: Xiaojun
authors: X
authors: Liu
authors: Regeneration Lab and Experimental Center of Life Sciences, School of Life Science, Shanghai University, Shanghai 200444, China.
authors: Junjie
authors: J
authors: Xiao
authors: Cardiovascular Division of the Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
authors: Han
authors: H
authors: Zhu
authors: Cardiovascular Division of the Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
authors: Xin
authors: X
authors: Wei
authors: Cardiovascular Division of the Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
authors: Colin
authors: C
authors: Platt
authors: Cardiovascular Division of the Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
authors: Federico
authors: F
authors: Damilano
authors: Cardiovascular Division of the Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
authors: Chunyang
authors: C
authors: Xiao
authors: Cardiovascular Division of the Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA; Cardiovascular Department of Boston Children's Hospital and Harvard Medical School, Boston, MA 02215, USA.
authors: Vassilios
authors: V
authors: Bezzerides
authors: Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
authors: Pontus
authors: P
authors: Boström
authors: Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
authors: Lin
authors: L
authors: Che
authors: Rush Medical College, Rush University, Chicago, IL 60612, USA.
authors: Chunxiang
authors: C
authors: Zhang
authors: Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, 02115, USA.
authors: Bruce M
authors: BM
authors: Spiegelman
authors: Cardiovascular Division of the Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA; Massachusetts General Hospital Cardiovascular Division and Harvard Medical School, Boston, MA 02115, USA. Electronic address: arosenzweig@partners.org.
authors: Anthony
authors: A
authors: Rosenzweig
mesh_terms: D000328:Adult; D000818:Animals; D064752:Atrial Remodeling / Q000502:physiology*; D049108:Cell Enlargement; D049109:Cell Proliferation / Q000502:physiology; D004452:Echocardiography; D006321:Heart / Q000254:growth & development*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D018613:Microscopy, Confocal; D008955:Models, Cardiovascular; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000502:physiology; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D015427:Reperfusion Injury / Q000628:therapy*
chemical_list: C546123:MIRN222 microRNA, mouse; D035683:MicroRNAs