IGF‐1 deficiency resists cardiac hypertrophy and myocardial contractile dysfunction: role of microRNA‐1 and microRNA‐133a

• Published in: Journal of cellular and molecular medicine Vol. 16; no. 1; pp. 83 - 95
• Main Authors: Hua, Yinan, Zhang, Yingmei, Ren, Jun
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.01.2012; John Wiley & Sons, Inc
• Subjects: Abdomen; AKT protein; Animals; Antibodies; Aorta; Atrial natriuretic peptide; Biomarkers - metabolism; Cardiac function; cardiac hypertrophy; Cardiomegaly - pathology; Cardiomegaly - physiopathology; Cardiomyocytes; Cell proliferation; Cell surface; Cells, Cultured; Coronary vessels; Cytology; Echocardiography; Gene expression; Glucose transporter; Glycogen; Glycogen synthase kinase 3; Heart failure; Heart Failure - pathology; Heart Failure - physiopathology; Heart Ventricles - pathology; Heart Ventricles - physiopathology; Hypertrophy; IGF‐1; Immunohistochemistry; Insulin-like growth factor I; Insulin-Like Growth Factor I - deficiency; Insulin-like growth factors; Kinases; Mice; Mice, Inbred C57BL; microRNA; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Muscle contraction; myocardial contraction; Myocardial Contraction - physiology; Myocytes, Cardiac - cytology; Myocytes, Cardiac - metabolism; Neonates; Original; Phosphorylation; Physiology; Protein deficiency; Protein phosphatase; Protein transport; Proteins; Rapamycin; Rats; TOR protein; Transfection; Ventricle; United States > US
• ISSN: 1582-1838; 1582-4934; 1582-4934
• DOI: 10.1111/j.1582-4934.2011.01307.x

This study was designed to examine the impact of insulin‐like growth factor‐1 (IGF‐1) deficiency on abdominal aortic constriction (AAC)‐induced cardiac geometric and functional changes with a focus on microRNA‐1, 133a and 208, which are specially expressed in hearts and govern cardiac hypertrophy and stress‐dependent cardiac growth. Liver‐specific IGF‐1‐deficient (LID) and C57/BL6 mice were subject to AAC. Echocardiographic and cardiomyocyte function were assessed 4 wks later. Haematoxylin and eosin staining was used to monitor myocardial morphology. Western blot and real‐time PCR were used to detect protein and miR expression, respectively. Neonatal rat cardiomyocytes (NRCMs) were transfected with miRs prior to IGF‐1 exposure to initiate cell proliferation. Immunohistochemistry and [3H] Leucine incorporation were used to detect cell surface area and protein abundance. C57 mice subject to AAC displayed increased ventricular wall thickness, decreased left ventricular end diastolic and end systolic dimensions and elevated cardiomyocyte shortening capacity, all of which were attenuated in LID mice. In addition, IGF‐1 deficiency mitigated AAC‐induced increase in atrial natriuretic factor, GATA binding protein 4, glucose transporter 4 (GLUT4) and Akt phosphorylation. In contrast, neither AAC treatment nor IGF‐1 deficiency affected glycogen synthase kinase 3b, mammalian target of rapamycin, the Glut‐4 translocation mediator Akt substrate of 160 kD (AS160) and protein phosphatase. Levels of miR‐1 and ‐133a (but not miR‐208) were significantly attenuated by AAC in C57 but not LID mice. Transfection of miR‐1 and ‐133a obliterated IGF‐1‐induced hypertrophic responses in NRCMs. Our data suggest that IGF‐1 deficiency retards AAC‐induced cardiac hypertrophic and contractile changes via alleviating down‐regulation of miR‐1 and miR‐133a in response to left ventricular pressure overload.