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Perilipin 5 is protective in the ischemic heart

Journal article
Authors Christina Drevinge
K. T. Dalen
M. N. Mannila
Margareta Scharin Täng
Marcus Ståhlman
Martina Klevstig
Annika Lundqvist
Ismena Mardani
F. Haugen
Per Fogelstrand
Martin Adiels
Jorge Asin-Cayuela
C. Ekestam
J. R. Gadin
Y. K. Lee
H. Nebb
Sara Svedlund
Bengt R Johansson
Lillemor Mattsson Hultén
Stefano Romeo
Björn Redfors
Elmir Omerovic
Max Levin
Li-Ming Gan
P. Eriksson
Linda Andersson
E. Ehrenborg
A. R. Kimmel
Jan Borén
Malin Levin
Published in International Journal of Cardiology
Volume 219
Pages 446-454
ISSN 0167-5273
Publication year 2016
Published at Wallenberg Laboratory
Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine
Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Institute of Medicine, Department of Molecular and Clinical Medicine
Pages 446-454
Language en
Links dx.doi.org/10.1016/j.ijcard.2016.06...
https://gup.ub.gu.se/file/199613
Keywords Myocardial ischemia, Lipid droplets, Perilipin 5, FATTY-ACID, MYOCARDIAL-INFARCTION, INSULIN-RESISTANCE, LIPID-METABOLISM, PROTEIN, MECHANISMS, PROMOTES, DISEASE, MUSCLE, OVEREXPRESSION
Subject categories Cardiovascular medicine

Abstract

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.

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