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)

Vol. 219 446-454

Subject Categories

Cardiac and Cardiovascular Systems

DOI

10.1016/j.ijcard.2016.06.037

More information

Created

10/10/2017