Journal article
Deletion of IGF-1 Receptors in Cardiomyocytes Attenuates Cardiac Aging in Male Mice
Endocrinology (Philadelphia), Vol.157(1), pp.336-345
01/2016
DOI: 10.1210/en.2015-1709
PMCID: PMC4701888
PMID: 26469138
Abstract
IGF-1 receptor (IGF-1R) signaling is implicated in cardiac hypertrophy and longevity. However, the role of IGF-1R in age-related cardiac remodeling is only partially understood. We therefore sought to determine whether the deletion of the IGF-1R in cardiomyocytes might delay the development of aging-associated myocardial pathologies by examining 2-year-old male cardiomyocyte-specific IGF-1R knockout (CIGF1RKO) mice. Aging was associated with the induction of IGF-1R expression in hearts. Cardiomyocytes hypertrophied with age in wild-type (WT) mice. In contrast, the cardiac hypertrophic response associated with aging was blunted in CIGF1RKO mice. Concomitantly, fibrosis was reduced in aged CIGF1RKO compared with aged WT hearts. Expression of proinflammatory cytokines such as IL-1α, IL-1β, IL-6, and receptor activator of nuclear factor-κB ligand was increased in aged WT hearts, but this increase was attenuated in aged CIGF1RKO hearts. Phosphorylation of Akt was increased in aged WT, but not in aged CIGF1RKO, hearts. In cultured cardiomyocytes, IGF-1 induced senescence as demonstrated by increased senescence-associated β-galactosidase staining, and a phosphoinositide 3-kinase inhibitor inhibited this effect. Furthermore, inhibition of phosphoinositide 3-kinase significantly prevented the increase in IL-1α, IL-1β, receptor activator of nuclear factor-κB ligand, and p21 protein expression by IGF-1. These data reveal an essential role for the IGF-1-IGF-1R-Akt pathway in mediating cardiomyocyte senescence.
Details
- Title: Subtitle
- Deletion of IGF-1 Receptors in Cardiomyocytes Attenuates Cardiac Aging in Male Mice
- Creators
- Sangmi Ock - Division of Endocrinology and Metabolism (S.O., J.A., H.M.K., J.K.), Department of Internal Medicine, Division of Cardiology (W.S.L.), Department of Internal Medicine, and Departments of Anesthesiology (H.K.) and Pathology (T.J.L.), College of Medicine, Chung-Ang University, Seoul, 156-755, Korea; Department of Biochemistry (H.-S.K.), College of Medicine, The Catholic University of Korea, Seoul, 110-758, Korea; Department of Surgery (D.J.), Vanderbilt University School of Medicine, Nashville, Tennessee 37232; and Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism (D.A.), University of Iowa Carver College of Medicine, Iowa City, Iowa 52242Wang Soo Lee - Division of Endocrinology and Metabolism (S.O., J.A., H.M.K., J.K.), Department of Internal Medicine, Division of Cardiology (W.S.L.), Department of Internal Medicine, and Departments of Anesthesiology (H.K.) and Pathology (T.J.L.), College of Medicine, Chung-Ang University, Seoul, 156-755, Korea; Department of Biochemistry (H.-S.K.), College of Medicine, The Catholic University of Korea, Seoul, 110-758, Korea; Department of Surgery (D.J.), Vanderbilt University School of Medicine, Nashville, Tennessee 37232; and Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism (D.A.), University of Iowa Carver College of Medicine, Iowa City, Iowa 52242Jihyun Ahn - Division of Endocrinology and Metabolism (S.O., J.A., H.M.K., J.K.), Department of Internal Medicine, Division of Cardiology (W.S.L.), Department of Internal Medicine, and Departments of Anesthesiology (H.K.) and Pathology (T.J.L.), College of Medicine, Chung-Ang University, Seoul, 156-755, Korea; Department of Biochemistry (H.-S.K.), College of Medicine, The Catholic University of Korea, Seoul, 110-758, Korea; Department of Surgery (D.J.), Vanderbilt University School of Medicine, Nashville, Tennessee 37232; and Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism (D.A.), University of Iowa Carver College of Medicine, Iowa City, Iowa 52242Hyun Min Kim - Division of Endocrinology and Metabolism (S.O., J.A., H.M.K., J.K.), Department of Internal Medicine, Division of Cardiology (W.S.L.), Department of Internal Medicine, and Departments of Anesthesiology (H.K.) and Pathology (T.J.L.), College of Medicine, Chung-Ang University, Seoul, 156-755, Korea; Department of Biochemistry (H.-S.K.), College of Medicine, The Catholic University of Korea, Seoul, 110-758, Korea; Department of Surgery (D.J.), Vanderbilt University School of Medicine, Nashville, Tennessee 37232; and Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism (D.A.), University of Iowa Carver College of Medicine, Iowa City, Iowa 52242Hyun Kang - Division of Endocrinology and Metabolism (S.O., J.A., H.M.K., J.K.), Department of Internal Medicine, Division of Cardiology (W.S.L.), Department of Internal Medicine, and Departments of Anesthesiology (H.K.) and Pathology (T.J.L.), College of Medicine, Chung-Ang University, Seoul, 156-755, Korea; Department of Biochemistry (H.-S.K.), College of Medicine, The Catholic University of Korea, Seoul, 110-758, Korea; Department of Surgery (D.J.), Vanderbilt University School of Medicine, Nashville, Tennessee 37232; and Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism (D.A.), University of Iowa Carver College of Medicine, Iowa City, Iowa 52242Ho-Shik Kim - Division of Endocrinology and Metabolism (S.O., J.A., H.M.K., J.K.), Department of Internal Medicine, Division of Cardiology (W.S.L.), Department of Internal Medicine, and Departments of Anesthesiology (H.K.) and Pathology (T.J.L.), College of Medicine, Chung-Ang University, Seoul, 156-755, Korea; Department of Biochemistry (H.-S.K.), College of Medicine, The Catholic University of Korea, Seoul, 110-758, Korea; Department of Surgery (D.J.), Vanderbilt University School of Medicine, Nashville, Tennessee 37232; and Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism (D.A.), University of Iowa Carver College of Medicine, Iowa City, Iowa 52242Daewoong Jo - Division of Endocrinology and Metabolism (S.O., J.A., H.M.K., J.K.), Department of Internal Medicine, Division of Cardiology (W.S.L.), Department of Internal Medicine, and Departments of Anesthesiology (H.K.) and Pathology (T.J.L.), College of Medicine, Chung-Ang University, Seoul, 156-755, Korea; Department of Biochemistry (H.-S.K.), College of Medicine, The Catholic University of Korea, Seoul, 110-758, Korea; Department of Surgery (D.J.), Vanderbilt University School of Medicine, Nashville, Tennessee 37232; and Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism (D.A.), University of Iowa Carver College of Medicine, Iowa City, Iowa 52242E Dale Abel - Division of Endocrinology and Metabolism (S.O., J.A., H.M.K., J.K.), Department of Internal Medicine, Division of Cardiology (W.S.L.), Department of Internal Medicine, and Departments of Anesthesiology (H.K.) and Pathology (T.J.L.), College of Medicine, Chung-Ang University, Seoul, 156-755, Korea; Department of Biochemistry (H.-S.K.), College of Medicine, The Catholic University of Korea, Seoul, 110-758, Korea; Department of Surgery (D.J.), Vanderbilt University School of Medicine, Nashville, Tennessee 37232; and Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism (D.A.), University of Iowa Carver College of Medicine, Iowa City, Iowa 52242Tae Jin Lee - Division of Endocrinology and Metabolism (S.O., J.A., H.M.K., J.K.), Department of Internal Medicine, Division of Cardiology (W.S.L.), Department of Internal Medicine, and Departments of Anesthesiology (H.K.) and Pathology (T.J.L.), College of Medicine, Chung-Ang University, Seoul, 156-755, Korea; Department of Biochemistry (H.-S.K.), College of Medicine, The Catholic University of Korea, Seoul, 110-758, Korea; Department of Surgery (D.J.), Vanderbilt University School of Medicine, Nashville, Tennessee 37232; and Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism (D.A.), University of Iowa Carver College of Medicine, Iowa City, Iowa 52242Jaetaek Kim - Division of Endocrinology and Metabolism (S.O., J.A., H.M.K., J.K.), Department of Internal Medicine, Division of Cardiology (W.S.L.), Department of Internal Medicine, and Departments of Anesthesiology (H.K.) and Pathology (T.J.L.), College of Medicine, Chung-Ang University, Seoul, 156-755, Korea; Department of Biochemistry (H.-S.K.), College of Medicine, The Catholic University of Korea, Seoul, 110-758, Korea; Department of Surgery (D.J.), Vanderbilt University School of Medicine, Nashville, Tennessee 37232; and Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism (D.A.), University of Iowa Carver College of Medicine, Iowa City, Iowa 52242
- Resource Type
- Journal article
- Publication Details
- Endocrinology (Philadelphia), Vol.157(1), pp.336-345
- Publisher
- United States
- DOI
- 10.1210/en.2015-1709
- PMID
- 26469138
- PMCID
- PMC4701888
- ISSN
- 0013-7227
- eISSN
- 1945-7170
- Grant note
- R01DK092065 / NIDDK NIH HHS R01 DK092065 / NIDDK NIH HHS
- Language
- English
- Date published
- 01/2016
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984024502402771
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