CPL - Chalmers Publication Library
| Utbildning | Forskning | Styrkeområden | Om Chalmers | In English In English Ej inloggad.

The VLDL Receptor Promotes Lipotoxicity and Increases Mortality in Mice Following an Acute Myocardial Infarction

Jeanna Perman ; Pontus Boström ; Malin Lindbom ; Ulf Lidberg ; Marcus Ståhlman ; Daniel Hägg (Institutionen för kemi- och bioteknik, Polymerteknologi) ; Henrik Lindskog ; Margareta Scharin Täng ; Elmir Omerovic ; Lillemor Mattsson Hultén ; Anders Jeppsson ; Petur Petursson ; Johan Herlitz ; Olivecrona G ; Kim Ekroos ; Sven-Olof Olofsson ; Jan Borén
Journal of Clinical Investigation (0021-9738). Vol. 121 (2011), 7, p. 2625-40.
[Artikel, refereegranskad vetenskaplig]

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.

Denna post skapades 2013-03-06. Senast ändrad 2016-08-31.
CPL Pubid: 174466


Läs direkt!

Länk till annan sajt (kan kräva inloggning)

Institutioner (Chalmers)

Institutionen för medicin (GU)
Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi (GU)
Institutionen för medicin, avdelningen för molekylär och klinisk medicin (GU)
Institutionen för kemi- och bioteknik, Polymerteknologi (2005-2014)
Institutionen för medicin, avdelningen för akut och kardiovaskulär medicin (2006-2011)
Wallenberglaboratoriet (GU)


Medicinsk cellbiologi

Chalmers infrastruktur