Adeno-Associated Virus Serotype 9–Driven Expression of BAG3 Improves Left Ventricular Function in Murine Hearts With Left Ventricular Dysfunction Secondary to a Myocardial Infarction

Tijana Knezevic; Valerie D. Myers; Feifei Su; Ju Fang Wang; Jianliang Song; Xue Qian Zhang; Erhe Gao; Guofeng Gao; Muniswamy Madesh; Manish K. Gupta; Jennifer Gordon; Kristen N. Weiner; Joseph Rabinowitz; Frederick V. Ramsey; Douglas G. Tilley; Kamel Khalili; Joseph Y. Cheung; Arthur M. Feldman

doi:10.1016/j.jacbts.2016.08.008

Adeno-Associated Virus Serotype 9–Driven Expression of BAG3 Improves Left Ventricular Function in Murine Hearts With Left Ventricular Dysfunction Secondary to a Myocardial Infarction

Tijana Knezevic, Valerie D. Myers, Feifei Su, Ju Fang Wang, Jianliang Song, Xue Qian Zhang, Erhe Gao, Guofeng Gao, Muniswamy Madesh, Manish K. Gupta, Jennifer Gordon, Kristen N. Weiner, Joseph Rabinowitz, Frederick V. Ramsey, Douglas G. Tilley, Kamel Khalili, Joseph Y. Cheung, Arthur M. Feldman

Producción científica: Review article › revisión exhaustiva

32 Citas (Scopus)

Resumen

Mutations in Bcl-2–associated athanogene 3 (BAG3) were associated with skeletal muscle dysfunction and dilated cardiomyopathy. Retro-orbital injection of an adeno-associated virus serotype 9 expressing BAG3 (rAAV9-BAG3) significantly (p < 0.0001) improved left ventricular ejection fraction, fractional shortening, and stroke volume 9 days post-injection in mice with cardiac dysfunction secondary to a myocardial infarction. Furthermore, myocytes isolated from mice 3 weeks after injection showed improved cell shortening, enhanced systolic [Ca²⁺]_i and increased [Ca²⁺]_i transient amplitudes, and increased maximal L-type Ca²⁺ current amplitude. These results suggest that BAG3 gene therapy may provide a novel therapeutic option for the treatment of heart failure.

Idioma original	English (US)
Páginas (desde-hasta)	647-656
Número de páginas	10
Publicación	JACC: Basic to Translational Science
Volumen	1
N.º	7
DOI	https://doi.org/10.1016/j.jacbts.2016.08.008
Estado	Published - 2016
Publicado de forma externa	Sí

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

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10.1016/j.jacbts.2016.08.008

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Knezevic, T., Myers, V. D., Su, F., Wang, J. F., Song, J., Zhang, X. Q., Gao, E., Gao, G., Madesh, M., Gupta, M. K., Gordon, J., Weiner, K. N., Rabinowitz, J., Ramsey, F. V., Tilley, D. G., Khalili, K., Cheung, J. Y., & Feldman, A. M. (2016). Adeno-Associated Virus Serotype 9–Driven Expression of BAG3 Improves Left Ventricular Function in Murine Hearts With Left Ventricular Dysfunction Secondary to a Myocardial Infarction. JACC: Basic to Translational Science, 1(7), 647-656. https://doi.org/10.1016/j.jacbts.2016.08.008

Adeno-Associated Virus Serotype 9–Driven Expression of BAG3 Improves Left Ventricular Function in Murine Hearts With Left Ventricular Dysfunction Secondary to a Myocardial Infarction. / Knezevic, Tijana; Myers, Valerie D.; Su, Feifei et al.
En: JACC: Basic to Translational Science, Vol. 1, N.º 7, 2016, p. 647-656.

Producción científica: Review article › revisión exhaustiva

Knezevic, T, Myers, VD, Su, F, Wang, JF, Song, J, Zhang, XQ, Gao, E, Gao, G, Madesh, M, Gupta, MK, Gordon, J, Weiner, KN, Rabinowitz, J, Ramsey, FV, Tilley, DG, Khalili, K, Cheung, JY & Feldman, AM 2016, 'Adeno-Associated Virus Serotype 9–Driven Expression of BAG3 Improves Left Ventricular Function in Murine Hearts With Left Ventricular Dysfunction Secondary to a Myocardial Infarction', JACC: Basic to Translational Science, vol. 1, n.º 7, pp. 647-656. https://doi.org/10.1016/j.jacbts.2016.08.008

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abstract = "Mutations in Bcl-2–associated athanogene 3 (BAG3) were associated with skeletal muscle dysfunction and dilated cardiomyopathy. Retro-orbital injection of an adeno-associated virus serotype 9 expressing BAG3 (rAAV9-BAG3) significantly (p < 0.0001) improved left ventricular ejection fraction, fractional shortening, and stroke volume 9 days post-injection in mice with cardiac dysfunction secondary to a myocardial infarction. Furthermore, myocytes isolated from mice 3 weeks after injection showed improved cell shortening, enhanced systolic [Ca2+]i and increased [Ca2+]i transient amplitudes, and increased maximal L-type Ca2+ current amplitude. These results suggest that BAG3 gene therapy may provide a novel therapeutic option for the treatment of heart failure.",

keywords = "BAG3, gene therapy, heart failure, left ventricular function, myocardial infarction",

author = "Tijana Knezevic and Myers, {Valerie D.} and Feifei Su and Wang, {Ju Fang} and Jianliang Song and Zhang, {Xue Qian} and Erhe Gao and Guofeng Gao and Muniswamy Madesh and Gupta, {Manish K.} and Jennifer Gordon and Weiner, {Kristen N.} and Joseph Rabinowitz and Ramsey, {Frederick V.} and Tilley, {Douglas G.} and Kamel Khalili and Cheung, {Joseph Y.} and Feldman, {Arthur M.}",

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doi = "10.1016/j.jacbts.2016.08.008",

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AU - Knezevic, Tijana

AU - Myers, Valerie D.

AU - Su, Feifei

AU - Wang, Ju Fang

AU - Song, Jianliang

AU - Zhang, Xue Qian

AU - Gao, Erhe

AU - Gao, Guofeng

AU - Madesh, Muniswamy

AU - Gupta, Manish K.

AU - Gordon, Jennifer

AU - Weiner, Kristen N.

AU - Rabinowitz, Joseph

AU - Ramsey, Frederick V.

AU - Tilley, Douglas G.

AU - Khalili, Kamel

AU - Cheung, Joseph Y.

AU - Feldman, Arthur M.

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N2 - Mutations in Bcl-2–associated athanogene 3 (BAG3) were associated with skeletal muscle dysfunction and dilated cardiomyopathy. Retro-orbital injection of an adeno-associated virus serotype 9 expressing BAG3 (rAAV9-BAG3) significantly (p < 0.0001) improved left ventricular ejection fraction, fractional shortening, and stroke volume 9 days post-injection in mice with cardiac dysfunction secondary to a myocardial infarction. Furthermore, myocytes isolated from mice 3 weeks after injection showed improved cell shortening, enhanced systolic [Ca2+]i and increased [Ca2+]i transient amplitudes, and increased maximal L-type Ca2+ current amplitude. These results suggest that BAG3 gene therapy may provide a novel therapeutic option for the treatment of heart failure.

AB - Mutations in Bcl-2–associated athanogene 3 (BAG3) were associated with skeletal muscle dysfunction and dilated cardiomyopathy. Retro-orbital injection of an adeno-associated virus serotype 9 expressing BAG3 (rAAV9-BAG3) significantly (p < 0.0001) improved left ventricular ejection fraction, fractional shortening, and stroke volume 9 days post-injection in mice with cardiac dysfunction secondary to a myocardial infarction. Furthermore, myocytes isolated from mice 3 weeks after injection showed improved cell shortening, enhanced systolic [Ca2+]i and increased [Ca2+]i transient amplitudes, and increased maximal L-type Ca2+ current amplitude. These results suggest that BAG3 gene therapy may provide a novel therapeutic option for the treatment of heart failure.

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KW - gene therapy

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KW - myocardial infarction

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