Perilipin 5 is protective in the ischemic heart
Artikel i vetenskaplig tidskrift, 2016
Background: Myocardial ischemia is associated with alterations in cardiac metabolism, resulting in decreased fatty acid oxidation and increased lipid accumulation. Here we investigate how myocardial lipid content and dynamics affect the function of the ischemic heart, and focus on the role of the lipid droplet protein perilipin 5 (Plin5) in the pathophysiology of myocardial ischemia. Methods and results: We generated Plin5(-/-) mice and found that Plin5 deficiency dramatically reduced the triglyceride content in the heart. Under normal conditions, Plin5(-/-) mice maintained a close to normal heart function by decreasing fatty acid uptake and increasing glucose uptake, thus preserving the energy balance. However, during stress or myocardial ischemia, Plin5 deficiency resulted in myocardial reduced substrate availability, severely reduced heart function and increased mortality. Importantly, analysis of a human cohort with suspected coronary artery disease showed that a common noncoding polymorphism, rs884164, decreases the cardiac expression of PLIN5 and is associated with reduced heart function following myocardial ischemia, indicating a role for Plin5 in cardiac dysfunction. Conclusion: Our findings indicate that Plin5 deficiency alters cardiac lipid metabolism and associates with reduced survival following myocardial ischemia, suggesting that Plin5 plays a beneficial role in the heart following ischemia. (C) 2016 The Authors. Published by Elsevier Ireland Ltd.
MUSCLE
MYOCARDIAL-INFARCTION
PROTEIN
PROMOTES
Myocardial ischemia
MECHANISMS
DISEASE
Lipid droplets
OVEREXPRESSION
INSULIN-RESISTANCE
FATTY-ACID
Perilipin 5
LIPID-METABOLISM
Författare
Christina Drevinge
Göteborgs universitet
K. T. Dalen
M. N. Mannila
Margareta Scharin Täng
Göteborgs universitet
Marcus Ståhlman
Göteborgs universitet
M. Klevstig
Göteborgs universitet
Annika Lundqvist
Göteborgs universitet
Ismena Mardani
Göteborgs universitet
F. Haugen
Per Fogelstrand
Göteborgs universitet
Martin Adiels
Göteborgs universitet
Jorge Asin-Cayuela
Göteborgs universitet
C. Ekestam
J. R. Gadin
Y. K. Lee
H. Nebb
Sara Svedlund
Göteborgs universitet
Bengt R Johansson
Göteborgs universitet
Lillemor Mattsson Hultén
Göteborgs universitet
Stefano Romeo
Göteborgs universitet
Björn Redfors
Göteborgs universitet
Elmir Omerovic
Göteborgs universitet
Max Levin
Göteborgs universitet
Li-Ming Gan
Göteborgs universitet
P. Eriksson
Linda Andersson
Göteborgs universitet
E. Ehrenborg
A. R. Kimmel
Jan Borén
Göteborgs universitet
Malin Levin
Göteborgs universitet
International Journal of Cardiology
0167-5273 (ISSN) 1874-1754 (eISSN)
Vol. 219 446-454Ämneskategorier
Kardiologi
DOI
10.1016/j.ijcard.2016.06.037