Perilipin 5 is protective in the ischemic heart

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• 作者：Christina Drevinge^a ; ^b ; Knut T. Dalen^c ; ^d ; ^e ; Maria Nastase Mannila^h ; Margareta Scharin Tä ; ng^a ; ^b ; Marcus Stå ; hlman^a ; ^b ; Martina Klevstig^a ; ^b ; Annika Lundqvist^a ; ^b ; Ismena Mardani^a ; ^b ; Fred Haugenⁱ ; Per Fogelstrand^a ; ^b ; Martin Adiels^a ; ^b ; Jorge Asin-Cayuela^j ; Charlotte Ekestam^h ; Jesper R. Gå ; din^h ; Yun K. Lee^e ; Hilde Nebb^d ; Sara Svedlund^a ; ^b ; Bengt R. Johansson^g ; Lillemor Mattsson Hulté ; n^a ; ^b ; Stefano Romeo^a ; ^b ; Bjö ; rn Redfors^a ; ^b ; Elmir Omerovic^a ; ^b ; Max Levin^a ; ^b ; Li-Ming Gan^a ; ^b ; ^f ; Per Eriksson^h ; Linda Andersson^a ; ^b ; Ewa Ehrenborg^h ; Alan R. Kimmel^e ; Jan Boré ; n^a ; ^b ; ¹ ; Malin C. Levin^a ; ^b ; ¹ ; ^{malin.levin@wlab.gu.se" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Myocardial ischemia ; Lipid droplets ; Perilipin 5
• 刊名：International Journal of Cardiology
• 出版年：2016
• 出版时间：15 September 2016
• 年：2016
• 卷：219
• 期：Complete
• 页码：446-454
• 全文大小：1006 K

文摘

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.