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 ∼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.
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 humanapolipoprotein AI shortened repolarization of isolated rabbit cardiomyocytes by ∼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.
Authors: Heather M Highland; Genevieve L Wojcik; Mariaelisa Graff; Katherine K Nishimura; Chani J Hodonsky; Antoine R Baldassari; Alanna C Cote; Iona Cheng; Christopher R Gignoux; Ran Tao; Yuqing Li; Eric Boerwinkle; Myriam Fornage; Jeffrey Haessler; Lucia A Hindorff; Yao Hu; Anne E Justice; Bridget M Lin; Danyu Lin; Daniel O Stram; Christopher A Haiman; Charles Kooperberg; Loic Le Marchand; Tara C Matise; Eimear E Kenny; Christopher S Carlson; Eli A Stahl; Christy L Avery; Kari E North; Jose Luis Ambite; Steven Buyske; Ruth J Loos; Ulrike Peters; Kristin L Young; Stephanie A Bien; Laura M Huckins Journal: Am J Hum Genet Date: 2022-03-08 Impact factor: 11.043
Authors: Stephanie C Gordts; Eline Van Craeyveld; Ilayaraja Muthuramu; Neha Singh; Frank Jacobs; Bart De Geest Journal: PLoS One Date: 2012-10-04 Impact factor: 3.240
Authors: Ruhul Amin; Ilayaraja Muthuramu; Joseph Pierre Aboumsallem; Mudit Mishra; Frank Jacobs; Bart De Geest Journal: Int J Mol Sci Date: 2017-09-20 Impact factor: 5.923