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Published on: October 3, 2019
Genetic and phenotypic targeting of β-adrenergic signaling in heart failure
1Center for Translational Medicine, Thomas Jefferson University, Philadelphia, PA, 19107, USA.
Insights
Heart failure prognosis remains poor. Genetic manipulation of beta-adrenergic receptor (β-AR) signaling, particularly inhibiting β-AR kinase (βARK1/GRK2), offers novel therapeutic strategies for heart failure.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Pharmacology
Background:
- Heart failure is a major cause of hospitalization with limited prognostic improvements.
- It is a common endpoint for diseases like hypertension and coronary artery disease.
- Altered beta-adrenergic receptor (β-AR) signaling is a key molecular feature of failing myocardium.
Purpose of the Study:
- To review β-AR signaling changes in heart failure.
- To discuss therapeutic strategies targeting β-AR signaling.
- To examine evidence for β-AR manipulation in heart failure treatment.
Main Methods:
- Review of existing literature on β-AR signaling in heart failure.
- Analysis of transgenic mouse models.
- Evaluation of in vivo gene therapy applications.
Main Results:
- Significant alterations in the β-AR signaling cascade are observed in heart failure.
- Transgenic studies support β-AR manipulation as a therapeutic approach.
- Gene therapy targeting β-AR signaling shows promise for reversing/preventing heart failure.
Conclusions:
- Targeting β-AR signaling, especially βARK1/GRK2, represents a novel therapeutic avenue for heart failure.
- Genetic manipulation offers potential for improved heart failure management.
- Further research into in vivo gene therapy is warranted.
Abstract:
Heart failure is a leading cause of hospitalization worldwide. No major significant improvements in prognosis have been achieved for heart failure over the last several decades despite advances in disease management. Heart failure itself represents a final common endpoint for several disease entities, including hypertension and coronary artery disease. On a molecular level, certain biochemical features remain common to failing myocardium. Among these are alterations in the β-adrenergic receptor (β-AR) signaling cascade. Recent advances in transgenic and gene therapy techniques have presented novel therapeutic strategies for management of heart failure via genetic manipulation of β-AR signaling including the targeted inhibition of the β-AR kinase (βARK1 or GRK2). In this review, we will discuss the β-AR signaling changes that accompany heart failure as well as corresponding therapeutic strategies. We will then review the evidence from transgenic mouse work supporting the use of β-AR manipulation in the failing heart and more recent in vivo applications of gene therapy directed at reversing or preventing heart failure. (Mol Cell Biochem 263: 5-9, 2004).
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