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Browsing by Author "Koch, WJ"
Now showing items 1-20 of 23
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Alterations in cardiac adrenergic signaling and calcium cycling differentially affect the progression of cardiomyopathy.
(J Clin Invest, 2001-04)The medical treatment of chronic heart failure has undergone a dramatic transition in the past decade. Short-term approaches for altering hemodynamics have given way to long-term, reparative strategies, including beta-adrenergic ... -
Cardiac beta ARK1 inhibition prolongs survival and augments beta blocker therapy in a mouse model of severe heart failure.
(Proc Natl Acad Sci U S A, 2001-05-08)Chronic human heart failure is characterized by abnormalities in beta-adrenergic receptor (betaAR) signaling, including increased levels of betaAR kinase 1 (betaARK1), which seems critical to the pathogenesis of the disease. ... -
Catecholamines, cardiac beta-adrenergic receptors, and heart failure.
(Circulation, 2000-04-11) -
Coupling of beta2-adrenoceptor to Gi proteins and its physiological relevance in murine cardiac myocytes.
(Circ Res, 1999-01-08)-Transgenic mouse models have been developed to manipulate beta-adrenergic receptor (betaAR) signal transduction. Although several of these models have altered betaAR subtypes, the specific functional sequelae of betaAR ... -
Direct evidence that Gi-coupled receptor stimulation of mitogen-activated protein kinase is mediated by G beta gamma activation of p21ras.
(Proc Natl Acad Sci U S A, 1994-12-20)Stimulation of Gi-coupled receptors leads to the activation of mitogen-activated protein kinases (MAP kinases). In several cell types, this appears to be dependent on the activation of p21ras (Ras). Which G-protein subunit(s) ... -
Dual modulation of cell survival and cell death by beta(2)-adrenergic signaling in adult mouse cardiac myocytes.
(Proc Natl Acad Sci U S A, 2001-02-13)The goal of this study was to determine whether beta(1)-adrenergic receptor (AR) and beta(2)-AR differ in regulating cardiomyocyte survival and apoptosis and, if so, to explore underlying mechanisms. One potential mechanism ... -
Enhancement of cardiac function after adenoviral-mediated in vivo intracoronary beta2-adrenergic receptor gene delivery.
(J Clin Invest, 1999-07)Exogenous gene delivery to alter the function of the heart is a potential novel therapeutic strategy for treatment of cardiovascular diseases such as heart failure (HF). Before gene therapy approaches to alter cardiac function ... -
Essential role of beta-adrenergic receptor kinase 1 in cardiac development and function.
(Proc Natl Acad Sci U S A, 1996-11-12)The beta-adrenergic receptor kinase 1 (beta ARK1) is a member of the G protein-coupled receptor kinase (GRK) family that mediates the agonist-dependent phosphorylation and desensitization of G protein-coupled receptors. ... -
Expression of a beta-adrenergic receptor kinase 1 inhibitor prevents the development of myocardial failure in gene-targeted mice.
(Proc Natl Acad Sci U S A, 1998-06-09)Heart failure is accompanied by severely impaired beta-adrenergic receptor (betaAR) function, which includes loss of betaAR density and functional uncoupling of remaining receptors. An important mechanism for the ... -
Functionally active targeting domain of the beta-adrenergic receptor kinase: an inhibitor of G beta gamma-mediated stimulation of type II adenylyl cyclase.
(Proc Natl Acad Sci U S A, 1994-04-26)The beta-adrenergic receptor kinase (beta ARK) phosphorylates its membrane-associated receptor substrates, such as the beta-adrenergic receptor, triggering events leading to receptor desensitization. beta ARK activity is ... -
G Protein Signaling and Vein Graft Intimal Hyperplasia: Reduction of Intimal Hyperplasia in Vein Grafts by a Gbg Inhibitor
(1998-08)Abstract—Vein grafting results in the development of intimal hyperplasia with accompanying changes in guanine nucleotide–binding (G) protein expression and function. Several serum mitogens that act through G protein–coupled ... -
Hybrid transgenic mice reveal in vivo specificity of G protein-coupled receptor kinases in the heart.
(Circ Res, 2000-01-07)G protein-coupled receptor kinases (GRKs) phosphorylate activated G protein-coupled receptors, including alpha(1B)-adrenergic receptors (ARs), resulting in desensitization. In vivo analysis of GRK substrate selectivity has ... -
In vivo inhibition of elevated myocardial beta-adrenergic receptor kinase activity in hybrid transgenic mice restores normal beta-adrenergic signaling and function.
(Circulation, 1999-08-10)BACKGROUND: The clinical syndrome of heart failure (HF) is characterized by an impaired cardiac beta-adrenergic receptor (betaAR) system, which is critical in the regulation of myocardial function. Expression of the betaAR ... -
In vivo ventricular gene delivery of a beta-adrenergic receptor kinase inhibitor to the failing heart reverses cardiac dysfunction.
(Circulation, 2001-03-06)BACKGROUND: Genetic manipulation to reverse molecular abnormalities associated with dysfunctional myocardium may provide novel treatment. This study aimed to determine the feasibility and functional consequences of in vivo ... -
Intracoronary Adenovirus-Mediated Delivery and Overexpression of the β2-Adrenergic Receptor in the Heart
(2000-02)Background—Genetic modulation of ventricular function may offer a novel therapeutic strategy for patients with congestive heart failure. Myocardial overexpression of β2-adrenergic receptors (β2ARs) has been shown to enhance ... -
Overexpression of the cardiac beta(2)-adrenergic receptor and expression of a beta-adrenergic receptor kinase-1 (betaARK1) inhibitor both increase myocardial contractility but have differential effects on susceptibility to ischemic injury.
(Circ Res, 1999-11-26)Cardiac beta(2)-adrenergic receptor (beta(2)AR) overexpression is a potential contractile therapy for heart failure. Cardiac contractility was elevated in mice overexpressing beta(2)ARs (TG4s) with no adverse effects under ... -
Potentiation of beta-adrenergic signaling by adenoviral-mediated gene transfer in adult rabbit ventricular myocytes.
(J Clin Invest, 1997-01-15)Our laboratory has been testing the hypothesis that genetic modulation of the beta-adrenergic signaling cascade can enhance cardiac function. We have previously shown that transgenic mice with cardiac overexpression of either ... -
Preservation of myocardial beta-adrenergic receptor signaling delays the development of heart failure after myocardial infarction.
(Proc Natl Acad Sci U S A, 2000-05-09)When the heart fails, there is often a constellation of biochemical alterations of the beta-adrenergic receptor (betaAR) signaling system, leading to the loss of cardiac inotropic reserve. betaAR down-regulation and functional ... -
Receptor-specific in vivo desensitization by the G protein-coupled receptor kinase-5 in transgenic mice.
(Proc Natl Acad Sci U S A, 1996-09-03)Transgenic mice were generated with cardiac-specific overexpression of the G protein-coupled receptor kinase-5 (GRK5), a serine/threonine kinase most abundantly expressed in the heart compared with other tissues. Animals ... -
Reciprocal in vivo regulation of myocardial G protein-coupled receptor kinase expression by beta-adrenergic receptor stimulation and blockade.
(Circulation, 1998-10-27)BACKGROUND: Impaired myocardial beta-adrenergic receptor (betaAR) signaling, including desensitization and functional uncoupling, is a characteristic of congestive heart failure. A contributing mechanism for this impairment ...
