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The VLDL receptor promotes lipotoxicity and increases mortality in mice following an acute myocardial infarction.

Perman, Jeanna, 1981 (author)
Gothenburg University,Göteborgs universitet,Institutionen för medicin,Institute of Medicine,University of Gothenburg
Boström, Pontus, 1982 (author)
Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory,University of Gothenburg
Lindbom, Malin, 1976 (author)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,University of Gothenburg
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Lidberg, Ulf, 1962 (author)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,University of Gothenburg
Ståhlman, Marcus, 1975 (author)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,University of Gothenburg
Hägg, Daniel, 1974 (author)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,University of Gothenburg
Lindskog, Henrik, 1977 (author)
Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology,University of Gothenburg
Scharin Täng, Margareta, 1962 (author)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,University of Gothenburg
Omerovic, Elmir, 1968 (author)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,University of Gothenburg
Mattsson Hultén, Lillemor, 1951 (author)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,University of Gothenburg
Jeppsson, Anders, 1960 (author)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,University of Gothenburg
Petursson, Petur, 1973 (author)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,University of Gothenburg
Herlitz, Johan, 1949 (author)
Högskolan i Borås,Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,University of Gothenburg,Institutionen för Vårdvetenskap
Olivecrona, Gunilla (author)
Umeå universitet,Fysiologisk kemi
Strickland, Dudley K (author)
Ekroos, Kim (author)
Olofsson, Sven-Olof, 1947 (author)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,University of Gothenburg
Borén, Jan, 1963 (author)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,University of Gothenburg
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 (creator_code:org_t)
American Society for Clinical Investigation, 2011
2011
English.
In: The Journal of clinical investigation. - : American Society for Clinical Investigation. - 1558-8238 .- 0021-9738. ; 121:7, s. 2625-40
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Impaired cardiac function is associated with myocardial triglyceride accumulation, but it is not clear how the lipids accumulate or whether this accumulation is detrimental. Here we show that hypoxia/ischemia-induced accumulation of lipids in HL-1 cardiomyocytes and mouse hearts is dependent on expression of the VLDL receptor (VLDLR). Hypoxia-induced VLDLR expression in HL-1 cells was dependent on HIF-1α through its interaction with a hypoxia-responsive element in the Vldlr promoter, and VLDLR promoted the endocytosis of lipoproteins. Furthermore, VLDLR expression was higher in ischemic compared with nonischemic left ventricles from human hearts and was correlated with the total lipid droplet area in the cardiomyocytes. Importantly, Vldlr-/- mice showed improved survival and decreased infarct area following an induced myocardial infarction. ER stress, which leads to apoptosis, is known to be involved in ischemic heart disease. We found that ischemia-induced ER stress and apoptosis in mouse hearts were reduced in Vldlr-/- mice and in mice treated with antibodies specific for VLDLR. These findings suggest that VLDLR-induced lipid accumulation in the ischemic heart worsens survival by increasing ER stress and apoptosis.

Keyword

Animals
Apoptosis
physiology
Cell Line
Endoplasmic Reticulum
metabolism
Humans
Lipid Metabolism
Lipids
chemistry
Mice
Mice
Inbred C57BL
Mice
Knockout
Myocardial Infarction
mortality
pathology
physiopathology
Myocardial Ischemia
mortality
pathology
physiopathology
Myocardium
cytology
metabolism
pathology
Receptors
LDL
genetics
metabolism
Stress
Physiological
Survival Rate
Triglycerides
toxicity
Survival Rate
Integrated Caring Science

Publication and Content Type

ref (subject category)
art (subject category)

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