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Review
. 2011 Mar 8;57(10):1169-80.
doi: 10.1016/j.jacc.2010.11.023.

Rescuing the failing heart by targeted gene transfer

Yoshiaki Kawase  1 , Dennis Ladage, Roger J Hajjar
Affiliations
Review

Rescuing the failing heart by targeted gene transfer

Yoshiaki Kawase et al. J Am Coll Cardiol. .

Abstract

Congestive heart failure is a major cause of morbidity and mortality in the United States. Although progress in conventional treatments is making steady and incremental gains to decrease heart failure mortality, there is a critical need to explore new therapeutic approaches. Gene therapy was initially applied in the clinical setting for inherited monogenic disorders. It is now apparent that gene therapy has broader potential that also includes acquired polygenic diseases, such as congestive heart failure. Recent advances in understanding of the molecular basis of myocardial dysfunction, together with the evolution of increasingly efficient gene transfer technology, have placed heart failure within the reach of gene-based therapy. Furthermore, the recent successful and safe completion of a phase 2 trial targeting the sarcoplasmic reticulum Ca(2+) ATPase pump along with the start of more recent phase 1 trials are ushering in a new era of gene therapy for the treatment of heart failure.

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Figures

Figure 1
Figure 1. Antegrade injections of Vectors through Coronary Vessels
a. Antegrade injection while blocking the coronary artery, b. Antegrade injection while blocking the coronary artery, c. recirculating flow,
Figure 1
Figure 1. Antegrade injections of Vectors through Coronary Vessels
a. Antegrade injection while blocking the coronary artery, b. Antegrade injection while blocking the coronary artery, c. recirculating flow,
Figure 1
Figure 1. Antegrade injections of Vectors through Coronary Vessels
a. Antegrade injection while blocking the coronary artery, b. Antegrade injection while blocking the coronary artery, c. recirculating flow,
Figure 2
Figure 2. Retrograde injections of Vectors through Coronary Vessels
a. Retrograde infusion through the coronary sinus, while the coronary artery is blocked; b: Intramyocardial injection from a catheter within the coronary vein.
Figure 2
Figure 2. Retrograde injections of Vectors through Coronary Vessels
a. Retrograde infusion through the coronary sinus, while the coronary artery is blocked; b: Intramyocardial injection from a catheter within the coronary vein.
Figure 3
Figure 3. Ventricular injections of Vectors
a. Direct surgical injections, b. Catheter based intracardiac injections, c. pericardial delivery.
Figure 3
Figure 3. Ventricular injections of Vectors
a. Direct surgical injections, b. Catheter based intracardiac injections, c. pericardial delivery.
Figure 3
Figure 3. Ventricular injections of Vectors
a. Direct surgical injections, b. Catheter based intracardiac injections, c. pericardial delivery.
Figure 4
Figure 4. Targets within Cardiac Myocytes
Excitation-contraction signaling in cardiomyoctyes with emphasis on targets for gene therapy. Interplay between Calcium handling (purple) and β-adrenergic (blue) systems is illustrated. AC: Adenylyl Cyclase; ATP: Adenosine Triphosphate; β-AR: Beta Adrenergic Receptor; I-1: (Protein Phosphatase) Inhibitor-1; cAMP: Cyclic Adenosine Monophosphate; Gs: Stimulatory G Protein; Gi: Inhibitory G Protein; NCX: Sarcolemnal Sodium/Calcium Exchanger; PKA: Protein Kinase A; PLN: Phospholamban; PP: Protein Phosphatase; RyR: Ryanodine Receptor; SERCA: Sarcoplasmic/Endoplasmic Reticulum Calcium ATPase; SR: Sarcoplasmic Reticulum.
See this image and copyright information in PMC

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