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Int J Cardiol. 2016 Sep 15;219:446-54. doi: 10.1016/j.ijcard.2016.06.037. Epub 2016 Jun 16.

Perilipin 5 is protective in the ischemic heart.

Author information

1
Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden; Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.
2
Norwegian Transgenic Center, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway; Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway; Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
3
Atherosclerosis Research Unit, Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
4
Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
5
Department of Clinical Chemistry, University of Gothenburg, Gothenburg, Sweden.
6
Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
7
Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
8
Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology, University of Gothenburg, Gothenburg, Sweden.
9
Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden; Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden; AstraZeneca R&D, Mölndal, Sweden.
10
Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden; Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden. Electronic address: malin.levin@wlab.gu.se.

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.

KEYWORDS:

Lipid droplets; Myocardial ischemia; Perilipin 5

PMID:
27376234
DOI:
10.1016/j.ijcard.2016.06.037
[Indexed for MEDLINE]
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