title: Cholesteryl esters accumulate in the heart in a porcine model of ischemia and reperfusion.
abstract: Myocardial ischemia is associated with intracellular accumulation of lipids and increased depots of myocardial lipids are linked to decreased heart function. Despite investigations in cell culture and animal models, there is little data available on where in the heart the lipids accumulate after myocardial ischemia and which lipid species that accumulate. The aim of this study was to investigate derangements of lipid metabolism that are associated with myocardial ischemia in a porcine model of ischemia and reperfusion. The large pig heart enables the separation of the infarct area with irreversible injury from the area at risk with reversible injury and the unaffected control area. The surviving myocardium bordering the infarct is exposed to mild ischemia and is stressed, but remains viable. We found that cholesteryl esters accumulated in the infarct area as well as in the bordering myocardium. In addition, we found that expression of the low density lipoprotein receptor (LDLr) and the low density lipoprotein receptor-related protein 1 (LRP1) was up-regulated, suggesting that choleteryl ester uptake is mediated via these receptors. Furthermore, we found increased ceramide accumulation, inflammation and endoplasmatic reticulum (ER) stress in the infarcted area of the pig heart. In addition, we found increased levels of inflammation and ER stress in the myocardium bordering the infarct area. Our results indicate that lipid accumulation in the heart is one of the metabolic derangements remaining after ischemia, even in the myocardium bordering the infarct area. Normalizing lipid levels in the myocardium after ischemia would likely improve myocardial function and should therefore be considered as a target for treatment.
authors: Wallenberg Laboratory, Sahlgrenska University Hospital, Göteborg, Sweden.
authors: Christina
authors: C
authors: Drevinge
authors: Lars O
authors: LO
authors: Karlsson
authors: Marcus
authors: M
authors: Ståhlman
authors: Thomas
authors: T
authors: Larsson
authors: Jeanna
authors: J
authors: Perman Sundelin
authors: Lars
authors: L
authors: Grip
authors: Linda
authors: L
authors: Andersson
authors: Jan
authors: J
authors: Borén
authors: Malin C
authors: MC
authors: Levin
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002518:Ceramides / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism*; D004195:Disease Models, Animal; D059865:Endoplasmic Reticulum Stress; D005260:Female; D007249:Inflammation / Q000209:etiology / Q000473:pathology; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D050356:Lipid Metabolism; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000378:metabolism; D009203:Myocardial Infarction / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D011973:Receptors, LDL / Q000378:metabolism; D034421:Sus scrofa
chemical_list: D015415:Biomarkers; D002518:Ceramides; D002788:Cholesterol Esters; D053583:Interleukin-1beta; D015850:Interleukin-6; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011973:Receptors, LDL
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