Reconstituted High-Density Lipoprotein Shortens Cardiac Repolarization

Hester M. Den Ruijter; Remco Franssen; Arie O. Verkerk; Diederik F. van Wijk; Stefan F. Vaessen; Adriaan G. Holleboom; Johannes H. Levels; Tobias Opthof; Rattapong Sungnoon; Erik S. Stroes; Jan Albert Kuivenhoven; Ruben Coronel

doi:10.1016/j.jacc.2010.11.072

Reconstituted High-Density Lipoprotein Shortens Cardiac Repolarization

Hester M. Den Ruijter, Remco Franssen, Arie O. Verkerk, Diederik F. van Wijk, Stefan F. Vaessen, Adriaan G. Holleboom, Johannes H. Levels, Tobias Opthof, Rattapong Sungnoon, Erik S. Stroes, Jan Albert Kuivenhoven, Ruben Coronel^*

^*Corresponding author for this work

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

Abstract

Objectives We hypothesize that increasing high-density lipoprotein cholesterol (HDL-C) shortens cardiac repolarization.

Background HDL-C is inversely associated with sudden death. The relation between HDL-C and repolarization of the heart is unexplored.

Methods HDL-C was elevated with reconstituted high-density lipoprotein (rHDL). Cardiac repolarization was studied by recording cardiac transmembrane potentials with the patch clamp technique from isolated rabbit cardiomyocytes that were superfused with rHDL. Infusions with rHDL (40 mg/kg body weight) were performed in dyslipidemic patients and healthy volunteers. Electrocardiograms were recorded to assess cardiac repolarization before and 24 h after infusion with rHDL.

Results rHDL as well as purified human apolipoprotein AI shortened repolarization of isolated rabbit cardiomyocytes by similar to 25% (p <0.05). rHDL infusion shortened the heart rate-corrected QT interval on surface electrocardiograms in all participants (p <0.001).

Conclusions rHDL shortens cardiac repolarization. These data provide evidence for a novel mechanism of HDL infusion that may contribute to reduction of sudden cardiac death. (J Am Coll Cardiol 2011;58:40-4) (C) 2011 by the American College of Cardiology Foundation

Original language	English
Pages (from-to)	40-44
Number of pages	5
Journal	Journal of the American College of Cardiology
Volume	58
Issue number	1
DOIs	https://doi.org/10.1016/j.jacc.2010.11.072
Publication status	Published - 28 Jun 2011

Keywords

action potential
ECG
electrophysiology
HDL-C
RANDOMIZED CONTROLLED-TRIAL
QT INTERVAL PROLONGATION
MYOCARDIAL-INFARCTION
SUDDEN-DEATH
CORONARY ATHEROSCLEROSIS
CARDIOVASCULAR MORTALITY
GENERAL-POPULATION
CHOLESTEROL
DISEASE
RABBITS

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10.1016/j.jacc.2010.11.072

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Den Ruijter, H. M., Franssen, R., Verkerk, A. O., van Wijk, D. F., Vaessen, S. F., Holleboom, A. G., Levels, J. H., Opthof, T., Sungnoon, R., Stroes, E. S., Kuivenhoven, J. A., & Coronel, R. (2011). Reconstituted High-Density Lipoprotein Shortens Cardiac Repolarization. Journal of the American College of Cardiology, 58(1), 40-44. https://doi.org/10.1016/j.jacc.2010.11.072

@article{042f0574ca834beab49abf9763e19f5d,

title = "Reconstituted High-Density Lipoprotein Shortens Cardiac Repolarization",

abstract = "Objectives We hypothesize that increasing high-density lipoprotein cholesterol (HDL-C) shortens cardiac repolarization.Background HDL-C is inversely associated with sudden death. The relation between HDL-C and repolarization of the heart is unexplored.Methods HDL-C was elevated with reconstituted high-density lipoprotein (rHDL). Cardiac repolarization was studied by recording cardiac transmembrane potentials with the patch clamp technique from isolated rabbit cardiomyocytes that were superfused with rHDL. Infusions with rHDL (40 mg/kg body weight) were performed in dyslipidemic patients and healthy volunteers. Electrocardiograms were recorded to assess cardiac repolarization before and 24 h after infusion with rHDL.Results rHDL as well as purified human apolipoprotein AI shortened repolarization of isolated rabbit cardiomyocytes by similar to 25% (p <0.05). rHDL infusion shortened the heart rate-corrected QT interval on surface electrocardiograms in all participants (p <0.001).Conclusions rHDL shortens cardiac repolarization. These data provide evidence for a novel mechanism of HDL infusion that may contribute to reduction of sudden cardiac death. (J Am Coll Cardiol 2011;58:40-4) (C) 2011 by the American College of Cardiology Foundation",

keywords = "action potential, ECG, electrophysiology, HDL-C, RANDOMIZED CONTROLLED-TRIAL, QT INTERVAL PROLONGATION, MYOCARDIAL-INFARCTION, SUDDEN-DEATH, CORONARY ATHEROSCLEROSIS, CARDIOVASCULAR MORTALITY, GENERAL-POPULATION, CHOLESTEROL, DISEASE, RABBITS",

author = "{Den Ruijter}, {Hester M.} and Remco Franssen and Verkerk, {Arie O.} and {van Wijk}, {Diederik F.} and Vaessen, {Stefan F.} and Holleboom, {Adriaan G.} and Levels, {Johannes H.} and Tobias Opthof and Rattapong Sungnoon and Stroes, {Erik S.} and Kuivenhoven, {Jan Albert} and Ruben Coronel",

year = "2011",

month = jun,

day = "28",

doi = "10.1016/j.jacc.2010.11.072",

language = "English",

volume = "58",

pages = "40--44",

journal = "Journal of the American College of Cardiology",

issn = "0735-1097",

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number = "1",

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TY - JOUR

T1 - Reconstituted High-Density Lipoprotein Shortens Cardiac Repolarization

AU - Den Ruijter, Hester M.

AU - Franssen, Remco

AU - Verkerk, Arie O.

AU - van Wijk, Diederik F.

AU - Vaessen, Stefan F.

AU - Holleboom, Adriaan G.

AU - Levels, Johannes H.

AU - Opthof, Tobias

AU - Sungnoon, Rattapong

AU - Stroes, Erik S.

AU - Kuivenhoven, Jan Albert

AU - Coronel, Ruben

PY - 2011/6/28

Y1 - 2011/6/28

N2 - Objectives We hypothesize that increasing high-density lipoprotein cholesterol (HDL-C) shortens cardiac repolarization.Background HDL-C is inversely associated with sudden death. The relation between HDL-C and repolarization of the heart is unexplored.Methods HDL-C was elevated with reconstituted high-density lipoprotein (rHDL). Cardiac repolarization was studied by recording cardiac transmembrane potentials with the patch clamp technique from isolated rabbit cardiomyocytes that were superfused with rHDL. Infusions with rHDL (40 mg/kg body weight) were performed in dyslipidemic patients and healthy volunteers. Electrocardiograms were recorded to assess cardiac repolarization before and 24 h after infusion with rHDL.Results rHDL as well as purified human apolipoprotein AI shortened repolarization of isolated rabbit cardiomyocytes by similar to 25% (p <0.05). rHDL infusion shortened the heart rate-corrected QT interval on surface electrocardiograms in all participants (p <0.001).Conclusions rHDL shortens cardiac repolarization. These data provide evidence for a novel mechanism of HDL infusion that may contribute to reduction of sudden cardiac death. (J Am Coll Cardiol 2011;58:40-4) (C) 2011 by the American College of Cardiology Foundation

AB - Objectives We hypothesize that increasing high-density lipoprotein cholesterol (HDL-C) shortens cardiac repolarization.Background HDL-C is inversely associated with sudden death. The relation between HDL-C and repolarization of the heart is unexplored.Methods HDL-C was elevated with reconstituted high-density lipoprotein (rHDL). Cardiac repolarization was studied by recording cardiac transmembrane potentials with the patch clamp technique from isolated rabbit cardiomyocytes that were superfused with rHDL. Infusions with rHDL (40 mg/kg body weight) were performed in dyslipidemic patients and healthy volunteers. Electrocardiograms were recorded to assess cardiac repolarization before and 24 h after infusion with rHDL.Results rHDL as well as purified human apolipoprotein AI shortened repolarization of isolated rabbit cardiomyocytes by similar to 25% (p <0.05). rHDL infusion shortened the heart rate-corrected QT interval on surface electrocardiograms in all participants (p <0.001).Conclusions rHDL shortens cardiac repolarization. These data provide evidence for a novel mechanism of HDL infusion that may contribute to reduction of sudden cardiac death. (J Am Coll Cardiol 2011;58:40-4) (C) 2011 by the American College of Cardiology Foundation

KW - action potential

KW - ECG

KW - electrophysiology

KW - HDL-C

KW - RANDOMIZED CONTROLLED-TRIAL

KW - QT INTERVAL PROLONGATION

KW - MYOCARDIAL-INFARCTION

KW - SUDDEN-DEATH

KW - CORONARY ATHEROSCLEROSIS

KW - CARDIOVASCULAR MORTALITY

KW - GENERAL-POPULATION

KW - CHOLESTEROL

KW - DISEASE

KW - RABBITS

U2 - 10.1016/j.jacc.2010.11.072

DO - 10.1016/j.jacc.2010.11.072

M3 - Article

C2 - 21700087

SN - 0735-1097

VL - 58

SP - 40

EP - 44

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

IS - 1

ER -

Reconstituted High-Density Lipoprotein Shortens Cardiac Repolarization

Abstract

Keywords

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