Perilipin 5 is protective in the ischemic heart
Journal article, 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
Author
Christina Drevinge
University of Gothenburg
K. T. Dalen
M. N. Mannila
Margareta Scharin Täng
University of Gothenburg
Marcus Ståhlman
University of Gothenburg
M. Klevstig
University of Gothenburg
Annika Lundqvist
University of Gothenburg
Ismena Mardani
University of Gothenburg
F. Haugen
Per Fogelstrand
University of Gothenburg
Martin Adiels
University of Gothenburg
Jorge Asin-Cayuela
University of Gothenburg
C. Ekestam
J. R. Gadin
Y. K. Lee
H. Nebb
Sara Svedlund
University of Gothenburg
Bengt R Johansson
University of Gothenburg
Lillemor Mattsson Hultén
University of Gothenburg
Stefano Romeo
University of Gothenburg
Björn Redfors
University of Gothenburg
Elmir Omerovic
University of Gothenburg
Max Levin
University of Gothenburg
Li-Ming Gan
University of Gothenburg
P. Eriksson
Linda Andersson
University of Gothenburg
E. Ehrenborg
A. R. Kimmel
Jan Borén
University of Gothenburg
Malin Levin
University of Gothenburg
International Journal of Cardiology
0167-5273 (ISSN) 1874-1754 (eISSN)
Vol. 219 446-454Subject Categories
Cardiac and Cardiovascular Systems
DOI
10.1016/j.ijcard.2016.06.037