Restoration of mechanical and energetic function in failing aortic-banded rat hearts by gene transfer of calcium cycling proteins

Susumu Sakata; Djamel Lebeche; Naoya Sakata; Yuri Sakata; Elie R. Chemaly; Li Fan Liang; Tsuyoshi Tsuji; Yoshiaki Takewa; Federica del Monte; Richard Peluso; Krisztina Zsebo; Dongtak Jeong; Woo Jin Park; Yoshiaki Kawase; Roger J. Hajjar

doi:10.1016/j.yjmcc.2007.01.003

Restoration of mechanical and energetic function in failing aortic-banded rat hearts by gene transfer of calcium cycling proteins

Susumu Sakata, Djamel Lebeche, Naoya Sakata, Yuri Sakata, Elie R. Chemaly, Li Fan Liang, Tsuyoshi Tsuji, Yoshiaki Takewa, Federica del Monte, Richard Peluso, Krisztina Zsebo, Dongtak Jeong, Woo Jin Park, Yoshiaki Kawase, Roger J. Hajjar

Research output: Contribution to journal › Article › peer-review

114 Scopus citations

Abstract

The aim of this study was to examine whether short- and long-term gene transfer of Ca²⁺ handling proteins restore left ventricular (LV) mechanoenergetics in aortic banding-induced failing hearts. Aortic-banded rats received recombinant adenoviruses carrying sarcoplasmic reticulum Ca²⁺-ATPase (SERCA2a) (Banding + SERCA), parvalbumin (Banding + Parv) or β-galactosidase (Banding + βgal), or an adeno-associated virus carrying SERCA2a (Banding + AAV.SERCA) by a catheter-based technique. LV mechanoenergetic function was measured in cross-circulated hearts. "Banding", "Banding + βgal" and "Banding + saline" groups showed lower end-systolic pressure at 0.1 ml intraballoon water (ESP_0.1), higher end-diastolic pressure at 0.1 ml intraballoon water (EDP_0.1) and slower LV relaxation rate, compared with "Normal" and "Sham". However, "Banding + SERCA" and "Banding + Parv" showed high ESP_0.1, low EDP_0.1 and fast LV relaxation rate. In "Banding", "Banding + βgal" and "Banding + saline", slope of relation between cardiac oxygen consumption and systolic pressure-volume area, O₂ cost of total mechanical energy, was twice higher than normal value, whereas slope in "Baning + SERCA" and "Banding + Parv" was similar to normal value. Furthermore, O₂ cost of LV contractility in the 3 control banding groups was ∼ 3 times higher than normal value, whereas O₂ cost of contractility in "Banding + SERCA", "Banding + AAV.SERCA" and "Banding + Parv" was as low as normal value. Thus, high O₂ costs of total mechanical energy and of LV contractility in failing hearts indicate energy wasting both in chemomechanical energy transduction and in calcium handling. Improved calcium handling by both short- and long-term overexpression of SERCA2a and parvalbumin transforms the inefficient energy utilization into a more efficient state. Therefore enhancement of calcium handling either by resequestration into the SR or by intracellular buffering improves not only mechanical but energetic function in failing hearts.

Original language	English
Pages (from-to)	852-861
Number of pages	10
Journal	Journal of Molecular and Cellular Cardiology
Volume	42
Issue number	4
DOIs	https://doi.org/10.1016/j.yjmcc.2007.01.003
State	Published - Apr 2007
Externally published	Yes

Keywords

Energetic function
Gene therapy
Heart failure
Parvalbumin
SERCA2a

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10.1016/j.yjmcc.2007.01.003

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Sakata, S., Lebeche, D., Sakata, N., Sakata, Y., Chemaly, E. R., Liang, L. F., Tsuji, T., Takewa, Y., del Monte, F., Peluso, R., Zsebo, K., Jeong, D., Park, W. J., Kawase, Y., & Hajjar, R. J. (2007). Restoration of mechanical and energetic function in failing aortic-banded rat hearts by gene transfer of calcium cycling proteins. Journal of Molecular and Cellular Cardiology, 42(4), 852-861. https://doi.org/10.1016/j.yjmcc.2007.01.003

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title = "Restoration of mechanical and energetic function in failing aortic-banded rat hearts by gene transfer of calcium cycling proteins",

abstract = "The aim of this study was to examine whether short- and long-term gene transfer of Ca2+ handling proteins restore left ventricular (LV) mechanoenergetics in aortic banding-induced failing hearts. Aortic-banded rats received recombinant adenoviruses carrying sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) (Banding + SERCA), parvalbumin (Banding + Parv) or β-galactosidase (Banding + βgal), or an adeno-associated virus carrying SERCA2a (Banding + AAV.SERCA) by a catheter-based technique. LV mechanoenergetic function was measured in cross-circulated hearts. {"}Banding{"}, {"}Banding + βgal{"} and {"}Banding + saline{"} groups showed lower end-systolic pressure at 0.1 ml intraballoon water (ESP0.1), higher end-diastolic pressure at 0.1 ml intraballoon water (EDP0.1) and slower LV relaxation rate, compared with {"}Normal{"} and {"}Sham{"}. However, {"}Banding + SERCA{"} and {"}Banding + Parv{"} showed high ESP0.1, low EDP0.1 and fast LV relaxation rate. In {"}Banding{"}, {"}Banding + βgal{"} and {"}Banding + saline{"}, slope of relation between cardiac oxygen consumption and systolic pressure-volume area, O2 cost of total mechanical energy, was twice higher than normal value, whereas slope in {"}Baning + SERCA{"} and {"}Banding + Parv{"} was similar to normal value. Furthermore, O2 cost of LV contractility in the 3 control banding groups was ∼ 3 times higher than normal value, whereas O2 cost of contractility in {"}Banding + SERCA{"}, {"}Banding + AAV.SERCA{"} and {"}Banding + Parv{"} was as low as normal value. Thus, high O2 costs of total mechanical energy and of LV contractility in failing hearts indicate energy wasting both in chemomechanical energy transduction and in calcium handling. Improved calcium handling by both short- and long-term overexpression of SERCA2a and parvalbumin transforms the inefficient energy utilization into a more efficient state. Therefore enhancement of calcium handling either by resequestration into the SR or by intracellular buffering improves not only mechanical but energetic function in failing hearts.",

keywords = "Energetic function, Gene therapy, Heart failure, Parvalbumin, SERCA2a",

author = "Susumu Sakata and Djamel Lebeche and Naoya Sakata and Yuri Sakata and Chemaly, {Elie R.} and Liang, {Li Fan} and Tsuyoshi Tsuji and Yoshiaki Takewa and {del Monte}, Federica and Richard Peluso and Krisztina Zsebo and Dongtak Jeong and Park, {Woo Jin} and Yoshiaki Kawase and Hajjar, {Roger J.}",

note = "Funding Information: This study was supported in part by grants from the National Institutes of Health: R01 HL078691, HL057263, HL071763, HL080498 and HL083156, and a Leducq Transatlantic Network (R.J.H.), K08 HL069842 (F.d.M.) and K01 HL076659 (D.L.).",

year = "2007",

month = apr,

doi = "10.1016/j.yjmcc.2007.01.003",

language = "English",

volume = "42",

pages = "852--861",

journal = "Journal of Molecular and Cellular Cardiology",

issn = "0022-2828",

publisher = "Academic Press",

number = "4",

}

Sakata, S, Lebeche, D, Sakata, N, Sakata, Y, Chemaly, ER, Liang, LF, Tsuji, T, Takewa, Y, del Monte, F, Peluso, R, Zsebo, K, Jeong, D, Park, WJ, Kawase, Y & Hajjar, RJ 2007, 'Restoration of mechanical and energetic function in failing aortic-banded rat hearts by gene transfer of calcium cycling proteins', Journal of Molecular and Cellular Cardiology, vol. 42, no. 4, pp. 852-861. https://doi.org/10.1016/j.yjmcc.2007.01.003

TY - JOUR

T1 - Restoration of mechanical and energetic function in failing aortic-banded rat hearts by gene transfer of calcium cycling proteins

AU - Sakata, Susumu

AU - Lebeche, Djamel

AU - Sakata, Naoya

AU - Sakata, Yuri

AU - Chemaly, Elie R.

AU - Liang, Li Fan

AU - Tsuji, Tsuyoshi

AU - Takewa, Yoshiaki

AU - del Monte, Federica

AU - Peluso, Richard

AU - Zsebo, Krisztina

AU - Jeong, Dongtak

AU - Park, Woo Jin

AU - Kawase, Yoshiaki

AU - Hajjar, Roger J.

N1 - Funding Information: This study was supported in part by grants from the National Institutes of Health: R01 HL078691, HL057263, HL071763, HL080498 and HL083156, and a Leducq Transatlantic Network (R.J.H.), K08 HL069842 (F.d.M.) and K01 HL076659 (D.L.).

PY - 2007/4

Y1 - 2007/4

N2 - The aim of this study was to examine whether short- and long-term gene transfer of Ca2+ handling proteins restore left ventricular (LV) mechanoenergetics in aortic banding-induced failing hearts. Aortic-banded rats received recombinant adenoviruses carrying sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) (Banding + SERCA), parvalbumin (Banding + Parv) or β-galactosidase (Banding + βgal), or an adeno-associated virus carrying SERCA2a (Banding + AAV.SERCA) by a catheter-based technique. LV mechanoenergetic function was measured in cross-circulated hearts. "Banding", "Banding + βgal" and "Banding + saline" groups showed lower end-systolic pressure at 0.1 ml intraballoon water (ESP0.1), higher end-diastolic pressure at 0.1 ml intraballoon water (EDP0.1) and slower LV relaxation rate, compared with "Normal" and "Sham". However, "Banding + SERCA" and "Banding + Parv" showed high ESP0.1, low EDP0.1 and fast LV relaxation rate. In "Banding", "Banding + βgal" and "Banding + saline", slope of relation between cardiac oxygen consumption and systolic pressure-volume area, O2 cost of total mechanical energy, was twice higher than normal value, whereas slope in "Baning + SERCA" and "Banding + Parv" was similar to normal value. Furthermore, O2 cost of LV contractility in the 3 control banding groups was ∼ 3 times higher than normal value, whereas O2 cost of contractility in "Banding + SERCA", "Banding + AAV.SERCA" and "Banding + Parv" was as low as normal value. Thus, high O2 costs of total mechanical energy and of LV contractility in failing hearts indicate energy wasting both in chemomechanical energy transduction and in calcium handling. Improved calcium handling by both short- and long-term overexpression of SERCA2a and parvalbumin transforms the inefficient energy utilization into a more efficient state. Therefore enhancement of calcium handling either by resequestration into the SR or by intracellular buffering improves not only mechanical but energetic function in failing hearts.

AB - The aim of this study was to examine whether short- and long-term gene transfer of Ca2+ handling proteins restore left ventricular (LV) mechanoenergetics in aortic banding-induced failing hearts. Aortic-banded rats received recombinant adenoviruses carrying sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) (Banding + SERCA), parvalbumin (Banding + Parv) or β-galactosidase (Banding + βgal), or an adeno-associated virus carrying SERCA2a (Banding + AAV.SERCA) by a catheter-based technique. LV mechanoenergetic function was measured in cross-circulated hearts. "Banding", "Banding + βgal" and "Banding + saline" groups showed lower end-systolic pressure at 0.1 ml intraballoon water (ESP0.1), higher end-diastolic pressure at 0.1 ml intraballoon water (EDP0.1) and slower LV relaxation rate, compared with "Normal" and "Sham". However, "Banding + SERCA" and "Banding + Parv" showed high ESP0.1, low EDP0.1 and fast LV relaxation rate. In "Banding", "Banding + βgal" and "Banding + saline", slope of relation between cardiac oxygen consumption and systolic pressure-volume area, O2 cost of total mechanical energy, was twice higher than normal value, whereas slope in "Baning + SERCA" and "Banding + Parv" was similar to normal value. Furthermore, O2 cost of LV contractility in the 3 control banding groups was ∼ 3 times higher than normal value, whereas O2 cost of contractility in "Banding + SERCA", "Banding + AAV.SERCA" and "Banding + Parv" was as low as normal value. Thus, high O2 costs of total mechanical energy and of LV contractility in failing hearts indicate energy wasting both in chemomechanical energy transduction and in calcium handling. Improved calcium handling by both short- and long-term overexpression of SERCA2a and parvalbumin transforms the inefficient energy utilization into a more efficient state. Therefore enhancement of calcium handling either by resequestration into the SR or by intracellular buffering improves not only mechanical but energetic function in failing hearts.

KW - Energetic function

KW - Gene therapy

KW - Heart failure

KW - Parvalbumin

KW - SERCA2a

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JO - Journal of Molecular and Cellular Cardiology

JF - Journal of Molecular and Cellular Cardiology

IS - 4

ER -

Restoration of mechanical and energetic function in failing aortic-banded rat hearts by gene transfer of calcium cycling proteins

Abstract

Keywords

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