AAV6-βARKct gene delivery mediated by molecular cardiac surgery with recirculating delivery (MCARD) in sheep results in robust gene expression and increased.

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Presentation transcript:

AAV6-βARKct gene delivery mediated by molecular cardiac surgery with recirculating delivery (MCARD) in sheep results in robust gene expression and increased adrenergic reserve Michael G. Katz, MD, PhD, Anthony S. Fargnoli, MS, JaBaris D. Swain, MD, Catherine E. Tomasulo, MD, Michele Ciccarelli, MD, Z. Maggie Huang, PhD, Joseph E. Rabinowitz, PhD, Charles R. Bridges, MD, ScD The Journal of Thoracic and Cardiovascular Surgery Volume 143, Issue 3, Pages 720-726.e3 (March 2012) DOI: 10.1016/j.jtcvs.2011.08.048 Copyright © 2012 The American Association for Thoracic Surgery Terms and Conditions

Figure 1 Effects of MCARD-βARKct gene transfer on LV mechanics. A, dP/dtmax. B, dP/dtmin. ∗P < .05; iso = 0.5 μg/min (dark bars) versus iso = 0 (light bars); †P < .05, 4 weeks versus control. The Journal of Thoracic and Cardiovascular Surgery 2012 143, 720-726.e3DOI: (10.1016/j.jtcvs.2011.08.048) Copyright © 2012 The American Association for Thoracic Surgery Terms and Conditions

Figure 2 A, Effect of MCARD-βARKct gene transfer on potential energy. ∗P < .05; iso = 0.5 μg/min (dark bars) versus iso = 0 (light bars). B, Effect of MCARD-βARKct gene transfer on arterial elastance ∗P < .05; iso = 0.5 μg/min (dark bars) versus iso = 0 (light bars). The Journal of Thoracic and Cardiovascular Surgery 2012 143, 720-726.e3DOI: (10.1016/j.jtcvs.2011.08.048) Copyright © 2012 The American Association for Thoracic Surgery Terms and Conditions

Figure 3 RT-qPCR: MCARD-βARKct left ventricle and collateral expression. The Journal of Thoracic and Cardiovascular Surgery 2012 143, 720-726.e3DOI: (10.1016/j.jtcvs.2011.08.048) Copyright © 2012 The American Association for Thoracic Surgery Terms and Conditions

Figure 4 A, MCARD-βARKct quantitative Western blot analysis: left and right ventricles versus lung and liver. B, MCARD-βARKct quantitative Western blot analysis: LV regional expression. C, MCARD-βARKct Western blot: left ventricle, lung, and liver. GAPDH, Glyceraldehyde-3-phosphate dehydrogenase; LV, left ventricular; RV, right ventricular. The Journal of Thoracic and Cardiovascular Surgery 2012 143, 720-726.e3DOI: (10.1016/j.jtcvs.2011.08.048) Copyright © 2012 The American Association for Thoracic Surgery Terms and Conditions

Figure 5 A, Cardiac cAMP level: MCARD-βARKct versus MCARD-GFP. B, Cardiac βAR density: MCARD-βARKct versus MCARD-GFP. The Journal of Thoracic and Cardiovascular Surgery 2012 143, 720-726.e3DOI: (10.1016/j.jtcvs.2011.08.048) Copyright © 2012 The American Association for Thoracic Surgery Terms and Conditions

Figure E1 A schematic of GRK2/βARKct protein constructs. βARKct, Carboxyl terminus of β-adrenergic receptor kinase. (modified from Brinks H, Koch WL. βARKct: a therapeutic approach for improved adrenergic signaling and function in heart disease. J Cardiovasc Trans Res. 2010;3:499-506.) The Journal of Thoracic and Cardiovascular Surgery 2012 143, 720-726.e3DOI: (10.1016/j.jtcvs.2011.08.048) Copyright © 2012 The American Association for Thoracic Surgery Terms and Conditions