Activation of IGF-2R stimulates cardiomyocyte hypertrophy in the late gestation sheep fetus

Kimberley C W Wang, Doug A. Brooks, Kent Thornburg, Janna L. Morrison

    Research output: Contribution to journalArticle

    18 Citations (Scopus)

    Abstract

    In vitro studies using rat and fetal sheep cardiomyocytes indicate that, in addition to its role as a clearance receptor, the insulin-like growth factor 2 receptor (IGF-2R) can induce cardiomyocyte hypertrophy. In the present study, we have determined the effect of specific activation of the IGF-2R in the heart of the late gestation fetus on cardiomyocyte development. Leu27IGF-2, an IGF-2R agonist, was infused into the fetal left circumflex coronary artery for 4 days beginning at 128.1 ± 0.4 days gestation. Ewes were humanely killed at 132.2 ± 1.2 days gestation (term, 150 days). Fetuses were delivered and hearts dissected to isolate the cardiomyocytes and to collect and snap-freeze tissue. Leu27IGF-2 infusion into the left circumflex coronary artery of fetal sheep increased the area of binucleated cardiomyocytes in the left, but not the right, ventricle. However, this infusion of Leu27IGF-2 did not change fetal weight, heart weight, blood pressure, blood gases or cardiomyocyte proliferation/binucleation. The increase in cardiomyocyte size in the Leu27IGF-2-infused group was associated with increased expression of proteins in the Gαs, but not the Gαq, signalling pathway. We concluded that infusion of Leu27IGF-2 into the left circumflex coronary artery causes cardiac IGF-2R activation in the left ventricle of the heart, and this stimulates cardiomyocyte hypertrophy in a Gαs-dependent manner.

    Original languageEnglish (US)
    Pages (from-to)5425-5437
    Number of pages13
    JournalJournal of Physiology
    Volume590
    Issue number21
    DOIs
    StatePublished - Nov 2012

    Fingerprint

    Somatomedin Receptors
    Cardiac Myocytes
    Hypertrophy
    Sheep
    Fetus
    Pregnancy
    Coronary Vessels
    Heart Ventricles
    Fetal Heart
    Fetal Weight
    Growth Factor Receptors
    Insulin Receptor
    Gases
    Blood Pressure
    Weights and Measures

    ASJC Scopus subject areas

    • Physiology

    Cite this

    Activation of IGF-2R stimulates cardiomyocyte hypertrophy in the late gestation sheep fetus. / Wang, Kimberley C W; Brooks, Doug A.; Thornburg, Kent; Morrison, Janna L.

    In: Journal of Physiology, Vol. 590, No. 21, 11.2012, p. 5425-5437.

    Research output: Contribution to journalArticle

    Wang, Kimberley C W ; Brooks, Doug A. ; Thornburg, Kent ; Morrison, Janna L. / Activation of IGF-2R stimulates cardiomyocyte hypertrophy in the late gestation sheep fetus. In: Journal of Physiology. 2012 ; Vol. 590, No. 21. pp. 5425-5437.
    @article{e2fb3389dcae4dbfa2ade1a8a4aecbb7,
    title = "Activation of IGF-2R stimulates cardiomyocyte hypertrophy in the late gestation sheep fetus",
    abstract = "In vitro studies using rat and fetal sheep cardiomyocytes indicate that, in addition to its role as a clearance receptor, the insulin-like growth factor 2 receptor (IGF-2R) can induce cardiomyocyte hypertrophy. In the present study, we have determined the effect of specific activation of the IGF-2R in the heart of the late gestation fetus on cardiomyocyte development. Leu27IGF-2, an IGF-2R agonist, was infused into the fetal left circumflex coronary artery for 4 days beginning at 128.1 ± 0.4 days gestation. Ewes were humanely killed at 132.2 ± 1.2 days gestation (term, 150 days). Fetuses were delivered and hearts dissected to isolate the cardiomyocytes and to collect and snap-freeze tissue. Leu27IGF-2 infusion into the left circumflex coronary artery of fetal sheep increased the area of binucleated cardiomyocytes in the left, but not the right, ventricle. However, this infusion of Leu27IGF-2 did not change fetal weight, heart weight, blood pressure, blood gases or cardiomyocyte proliferation/binucleation. The increase in cardiomyocyte size in the Leu27IGF-2-infused group was associated with increased expression of proteins in the Gαs, but not the Gαq, signalling pathway. We concluded that infusion of Leu27IGF-2 into the left circumflex coronary artery causes cardiac IGF-2R activation in the left ventricle of the heart, and this stimulates cardiomyocyte hypertrophy in a Gαs-dependent manner.",
    author = "Wang, {Kimberley C W} and Brooks, {Doug A.} and Kent Thornburg and Morrison, {Janna L.}",
    year = "2012",
    month = "11",
    doi = "10.1113/jphysiol.2012.238410",
    language = "English (US)",
    volume = "590",
    pages = "5425--5437",
    journal = "Journal of Physiology",
    issn = "0022-3751",
    publisher = "Wiley-Blackwell",
    number = "21",

    }

    TY - JOUR

    T1 - Activation of IGF-2R stimulates cardiomyocyte hypertrophy in the late gestation sheep fetus

    AU - Wang, Kimberley C W

    AU - Brooks, Doug A.

    AU - Thornburg, Kent

    AU - Morrison, Janna L.

    PY - 2012/11

    Y1 - 2012/11

    N2 - In vitro studies using rat and fetal sheep cardiomyocytes indicate that, in addition to its role as a clearance receptor, the insulin-like growth factor 2 receptor (IGF-2R) can induce cardiomyocyte hypertrophy. In the present study, we have determined the effect of specific activation of the IGF-2R in the heart of the late gestation fetus on cardiomyocyte development. Leu27IGF-2, an IGF-2R agonist, was infused into the fetal left circumflex coronary artery for 4 days beginning at 128.1 ± 0.4 days gestation. Ewes were humanely killed at 132.2 ± 1.2 days gestation (term, 150 days). Fetuses were delivered and hearts dissected to isolate the cardiomyocytes and to collect and snap-freeze tissue. Leu27IGF-2 infusion into the left circumflex coronary artery of fetal sheep increased the area of binucleated cardiomyocytes in the left, but not the right, ventricle. However, this infusion of Leu27IGF-2 did not change fetal weight, heart weight, blood pressure, blood gases or cardiomyocyte proliferation/binucleation. The increase in cardiomyocyte size in the Leu27IGF-2-infused group was associated with increased expression of proteins in the Gαs, but not the Gαq, signalling pathway. We concluded that infusion of Leu27IGF-2 into the left circumflex coronary artery causes cardiac IGF-2R activation in the left ventricle of the heart, and this stimulates cardiomyocyte hypertrophy in a Gαs-dependent manner.

    AB - In vitro studies using rat and fetal sheep cardiomyocytes indicate that, in addition to its role as a clearance receptor, the insulin-like growth factor 2 receptor (IGF-2R) can induce cardiomyocyte hypertrophy. In the present study, we have determined the effect of specific activation of the IGF-2R in the heart of the late gestation fetus on cardiomyocyte development. Leu27IGF-2, an IGF-2R agonist, was infused into the fetal left circumflex coronary artery for 4 days beginning at 128.1 ± 0.4 days gestation. Ewes were humanely killed at 132.2 ± 1.2 days gestation (term, 150 days). Fetuses were delivered and hearts dissected to isolate the cardiomyocytes and to collect and snap-freeze tissue. Leu27IGF-2 infusion into the left circumflex coronary artery of fetal sheep increased the area of binucleated cardiomyocytes in the left, but not the right, ventricle. However, this infusion of Leu27IGF-2 did not change fetal weight, heart weight, blood pressure, blood gases or cardiomyocyte proliferation/binucleation. The increase in cardiomyocyte size in the Leu27IGF-2-infused group was associated with increased expression of proteins in the Gαs, but not the Gαq, signalling pathway. We concluded that infusion of Leu27IGF-2 into the left circumflex coronary artery causes cardiac IGF-2R activation in the left ventricle of the heart, and this stimulates cardiomyocyte hypertrophy in a Gαs-dependent manner.

    UR - http://www.scopus.com/inward/record.url?scp=84868103395&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=84868103395&partnerID=8YFLogxK

    U2 - 10.1113/jphysiol.2012.238410

    DO - 10.1113/jphysiol.2012.238410

    M3 - Article

    C2 - 22930271

    AN - SCOPUS:84868103395

    VL - 590

    SP - 5425

    EP - 5437

    JO - Journal of Physiology

    JF - Journal of Physiology

    SN - 0022-3751

    IS - 21

    ER -