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Cardiology

Thomas Jefferson University

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Mice

Articles 1 - 7 of 7

Full-Text Articles in Medicine and Health Sciences

Determining The Absolute Requirement Of G Protein-Coupled Receptor Kinase 5 For Pathological Cardiac Hypertrophy: Short Communication., Jessica I Gold, Erhe Gao, Xiying Shang, Richard T Premont, Walter J Koch Sep 2012

Determining The Absolute Requirement Of G Protein-Coupled Receptor Kinase 5 For Pathological Cardiac Hypertrophy: Short Communication., Jessica I Gold, Erhe Gao, Xiying Shang, Richard T Premont, Walter J Koch

Center for Translational Medicine Faculty Papers

RATIONALE: Heart failure (HF) is often the end phase of maladaptive cardiac hypertrophy. A contributing factor is activation of a hypertrophic gene expression program controlled by decreased class II histone deacetylase (HDAC) transcriptional repression via HDAC phosphorylation. Cardiac-specific overexpression of G proteinen-coupled receptor kinase-5 (GRK5) has previously been shown to possess nuclear activity as a HDAC5 kinase, promoting an intolerance to in vivo ventricular pressure overload; however, its endogenous requirement in adaptive and maladaptive hypertrophy remains unknown.

OBJECTIVE: We used mouse models with global or cardiomyocyte-specific GRK5 gene deletion to determine the absolute requirement of endogenous GRK5 for cardiac hypertrophy …


Cardiac G-Protein-Coupled Receptor Kinase 2 Ablation Induces A Novel Ca2+ Handling Phenotype Resistant To Adverse Alterations And Remodeling After Myocardial Infarction., Philip W Raake, Xiaoying Zhang, Leif E Vinge, Henriette Brinks, Erhe Gao, Naser Jaleel, Yingxin Li, Mingxin Tang, Patrick Most, Gerald W Dorn, Steven R Houser, Hugo A Katus, Xiongwen Chen, Walter J Koch May 2012

Cardiac G-Protein-Coupled Receptor Kinase 2 Ablation Induces A Novel Ca2+ Handling Phenotype Resistant To Adverse Alterations And Remodeling After Myocardial Infarction., Philip W Raake, Xiaoying Zhang, Leif E Vinge, Henriette Brinks, Erhe Gao, Naser Jaleel, Yingxin Li, Mingxin Tang, Patrick Most, Gerald W Dorn, Steven R Houser, Hugo A Katus, Xiongwen Chen, Walter J Koch

Center for Translational Medicine Faculty Papers

BACKGROUND: G-protein-coupled receptor kinase 2 (GRK2) is a primary regulator of β-adrenergic signaling in the heart. G-protein-coupled receptor kinase 2 ablation impedes heart failure development, but elucidation of the cellular mechanisms has not been achieved, and such elucidation is the aim of this study.

METHODS AND RESULTS: Myocyte contractility, Ca(2+) handling and excitation-contraction coupling were studied in isolated cardiomyocytes from wild-type and GRK2 knockout (GRK2KO) mice without (sham) or with myocardial infarction (MI). In cardiac myocytes isolated from unstressed wild-type and GRK2KO hearts, myocyte contractions and Ca(2+) transients were similar, but GRK2KO myocytes had lower sarcoplasmic reticulum (SR) Ca(2+) content …


Hyperphosphorylation Of The Cardiac Ryanodine Receptor At Serine 2808 Is Not Involved In Cardiac Dysfunction After Myocardial Infarction., Hongyu Zhang, Catherine A Makarewich, Hajime Kubo, Wei Wang, Jason M Duran, Ying Li, Remus M Berretta, Walter J Koch, Xiongwen Chen, Erhe Gao, Héctor H Valdivia, Steven R Houser Mar 2012

Hyperphosphorylation Of The Cardiac Ryanodine Receptor At Serine 2808 Is Not Involved In Cardiac Dysfunction After Myocardial Infarction., Hongyu Zhang, Catherine A Makarewich, Hajime Kubo, Wei Wang, Jason M Duran, Ying Li, Remus M Berretta, Walter J Koch, Xiongwen Chen, Erhe Gao, Héctor H Valdivia, Steven R Houser

Division of Cardiology Faculty Papers

RATIONALE: Abnormal behavior of the cardiac ryanodine receptor (RyR2) has been linked to cardiac arrhythmias and heart failure (HF) after myocardial infarction (MI). It has been proposed that protein kinase A (PKA) hyperphosphorylation of the RyR2 at a single residue, Ser-2808, is a critical mediator of RyR dysfunction, depressed cardiac performance, and HF after MI.

OBJECTIVE: We used a mouse model (RyRS2808A) in which PKA hyperphosphorylation of the RyR2 at Ser-2808 is prevented to determine whether loss of PKA phosphorylation at this site averts post MI cardiac pump dysfunction.

METHODS AND RESULTS: MI was induced in wild-type (WT) and S2808A …


Cardioprotection Of Controlled And Cardiac-Specific Over-Expression Of A(2a)-Adenosine Receptor In The Pressure Overload., Eman A Hamad, Weizhong Zhu, Tung O Chan, Valerie Myers, Erhe Gao, Xue Li, Jin Zhang, Jianliang Song, Xue-Qian Zhang, Joseph Y Cheung, Walter Koch, Arthur M Feldman Jan 2012

Cardioprotection Of Controlled And Cardiac-Specific Over-Expression Of A(2a)-Adenosine Receptor In The Pressure Overload., Eman A Hamad, Weizhong Zhu, Tung O Chan, Valerie Myers, Erhe Gao, Xue Li, Jin Zhang, Jianliang Song, Xue-Qian Zhang, Joseph Y Cheung, Walter Koch, Arthur M Feldman

Center for Translational Medicine Faculty Papers

Adenosine binds to three G protein-coupled receptors (R) located on the cardiomyocyte (A(1)-R, A(2A)-R and A(3)-R) and provides cardiac protection during both ischemic and load-induced stress. While the role of adenosine receptor-subtypes has been well defined in the setting of ischemia-reperfusion, far less is known regarding their roles in protecting the heart during other forms of cardiac stress. Because of its ability to increase cardiac contractility and heart rate, we hypothesized that enhanced signaling through A(2A)-R would protect the heart during the stress of transverse aortic constriction (TAC). Using a cardiac-specific and inducible promoter, we selectively over-expressed A(2A)-R in FVB …


Wnt Signaling Exerts An Antiproliferative Effect On Adult Cardiac Progenitor Cells Through Igfbp3., Angelos Oikonomopoulos, Konstantina-Ioanna Sereti, Frank Conyers, Michael Bauer, Annette Liao, Jian Guan, Dylan Crapps, Jung-Kyu Han, Hanhua Dong, Ahmad F Bayomy, Gabriel C Fine, Karen Westerman, Travis L Biechele, Randall T Moon, Thomas Force, Ronglih Liao Dec 2011

Wnt Signaling Exerts An Antiproliferative Effect On Adult Cardiac Progenitor Cells Through Igfbp3., Angelos Oikonomopoulos, Konstantina-Ioanna Sereti, Frank Conyers, Michael Bauer, Annette Liao, Jian Guan, Dylan Crapps, Jung-Kyu Han, Hanhua Dong, Ahmad F Bayomy, Gabriel C Fine, Karen Westerman, Travis L Biechele, Randall T Moon, Thomas Force, Ronglih Liao

Center for Translational Medicine Faculty Papers

RATIONALE: Recent work in animal models and humans has demonstrated the presence of organ-specific progenitor cells required for the regenerative capacity of the adult heart. In response to tissue injury, progenitor cells differentiate into specialized cells, while their numbers are maintained through mechanisms of self-renewal. The molecular cues that dictate the self-renewal of adult progenitor cells in the heart, however, remain unclear.

OBJECTIVE: We investigate the role of canonical Wnt signaling on adult cardiac side population (CSP) cells under physiological and disease conditions.

METHODS AND RESULTS: CSP cells isolated from C57BL/6J mice were used to study the effects of canonical …


Gsk-3alpha Directly Regulates Beta-Adrenergic Signaling And The Response Of The Heart To Hemodynamic Stress In Mice., Jibin Zhou, Hind Lal, Xiongwen Chen, Xiying Shang, Jianliang Song, Yingxin Li, Risto Kerkela, Bradley W Doble, Katrina Macaulay, Morgan Decaul, Walter J Koch, John Farber, James Woodgett, Erhe Gao, Thomas Force Jul 2010

Gsk-3alpha Directly Regulates Beta-Adrenergic Signaling And The Response Of The Heart To Hemodynamic Stress In Mice., Jibin Zhou, Hind Lal, Xiongwen Chen, Xiying Shang, Jianliang Song, Yingxin Li, Risto Kerkela, Bradley W Doble, Katrina Macaulay, Morgan Decaul, Walter J Koch, John Farber, James Woodgett, Erhe Gao, Thomas Force

Center for Translational Medicine Faculty Papers

The glycogen synthase kinase-3 (GSK-3) family of serine/threonine kinases consists of 2 highly related isoforms, alpha and beta. Although GSK-3beta has an important role in cardiac development, much remains unknown about the function of either GSK-3 isoform in the postnatal heart. Herein, we present what we believe to be the first studies defining the role of GSK-3alpha in the mouse heart using gene targeting. Gsk3a(-/-) mice over 2 months of age developed progressive cardiomyocyte and cardiac hypertrophy and contractile dysfunction. Following thoracic aortic constriction in young mice, we observed enhanced hypertrophy that rapidly transitioned to ventricular dilatation and contractile dysfunction. …


P5l Mutation In Ank Results In An Increase In Extracellular Inorganic Pyrophosphate During Proliferation And Nonmineralizing Hypertrophy In Stably Transduced Atdc5 Cells, Raihana Zaka, David Stokes, Arnold S. Dion, Anna Kusnierz, Fei Han, Charlene J. Williams Oct 2006

P5l Mutation In Ank Results In An Increase In Extracellular Inorganic Pyrophosphate During Proliferation And Nonmineralizing Hypertrophy In Stably Transduced Atdc5 Cells, Raihana Zaka, David Stokes, Arnold S. Dion, Anna Kusnierz, Fei Han, Charlene J. Williams

Center for Translational Medicine Faculty Papers

Ank is a multipass transmembrane protein that regulates the cellular transport of inorganic pyrophosphate. In the progressive ankylosis (ank) mouse, a premature termination mutation at glutamic acid 440 results in a phenotype characterized by inappropriate deposition of basic calcium phosphate crystals in skeletal tissues. Mutations in the amino terminus of ANKH, the human homolog of Ank, result in familial calcium pyrophosphate dihydrate deposition disease. It has been hypothesized that these mutations result in a gain-of-function with respect to the elaboration of extracellular inorganic pyrophosphate. To explore this issue in a mineralization-competent system, we stably transduced ATDC5 cells with wild-type Ank …