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Review
. 2010 Summer;22(2):127-39.
doi: 10.1053/j.semtcvs.2010.09.009.

Cardiac gene therapy

Antoine H Chaanine  1 , Jill Kalman, Roger J Hajjar
Affiliations
Review

Cardiac gene therapy

Antoine H Chaanine et al. Semin Thorac Cardiovasc Surg. 2010 Summer.

Abstract

Heart failure is a chronic progressive disorder in which frequent and recurrent hospitalizations are associated with high mortality and morbidity. The incidence and the prevalence of this disease will increase with the increase in the number of the aging population of the United States. Understanding the molecular pathology and pathophysiology of this disease will uncover novel targets and therapies that can restore the function or attenuate the damage of malfunctioning cardiomyocytes by gene therapy that becomes an interesting and a promising field for the treatment of heart failure as well as other diseases in the future. Of equal importance are developing vectors and delivery methods that can efficiently transduce most of the cardiomyocytes that can offer a long-term expression and that can escape the host immune response. Recombinant adeno-associated virus vectors have the potential to become a promising novel therapeutic vehicles for molecular medicine in the future.

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Figures

Figure 1
Figure 1
A. Electron microscopy image showing the ultrustructural architecture of the cardiomyocyte. B. is a schematic illustration of the T-tubules (T), junctional sarcoplasmic reticulum (JSR). mitochondria and sarcomere. Note mat these structures are found in close proximity and are considered organelles of high calcium domain in the cardiomyocyte.
Figure 2
Figure 2. Calcium Ion Flux during the contraction-relaxation phase of the cardiac cycle
As the depolarization wave reaches the L-type calcium channels, calcium enters the cardiomyocyte triggering release of ca from the SR. Calcium binds to troponin C leading to contraction of the Cardiomyocyte. The Increase in intracellular ca activates SERCA 2a that pumps Ca into the SR so that relaxation takes place and the cell is ready for the next cardiac cycle.
Figure 3
Figure 3
changes in calcium handling proteins in heart failure. There is (1) downregulation and hyperphosphorylation of LTCC by β-ARKct, (2) hyperphosphorylation of RYR receptors and increase calcium leak from the JSR into the cytoplasm. (3) hypo-Phosphorylation of PLB, (4) downregulation of SERCA2a and depletion of SR Ca stores. (5) upregulation of NCX-1 receptors.
Figure 4
Figure 4
Potential gene therapy targets for the treatment of heart failure.
See this image and copyright information in PMC

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