1. Perilipin 5 is protective in the ischemic heart.
- Author
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Drevinge C, Dalen KT, Mannila MN, Täng MS, Ståhlman M, Klevstig M, Lundqvist A, Mardani I, Haugen F, Fogelstrand P, Adiels M, Asin-Cayuela J, Ekestam C, Gådin JR, Lee YK, Nebb H, Svedlund S, Johansson BR, Hultén LM, Romeo S, Redfors B, Omerovic E, Levin M, Gan LM, Eriksson P, Andersson L, Ehrenborg E, Kimmel AR, Borén J, and Levin MC
- Subjects
- Animals, Coronary Artery Disease blood, Coronary Artery Disease genetics, Coronary Artery Disease prevention & control, Female, Humans, Intracellular Signaling Peptides and Proteins genetics, Male, Mice, Mice, Knockout, Muscle Proteins genetics, Myocardial Ischemia genetics, Myocardium metabolism, Myocardium pathology, Triglycerides blood, Intracellular Signaling Peptides and Proteins deficiency, Muscle Proteins deficiency, Myocardial Ischemia blood, Myocardial Ischemia prevention & control
- 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., (Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)
- Published
- 2016
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