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)

Vol. 219 446-454

Ämneskategorier

Kardiologi

DOI

10.1016/j.ijcard.2016.06.037