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- Aminoff, A, et al.
(author)
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Allele-specific regulation of MTTP expression influences the risk of ischemic heart disease.
- 2010
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In: Journal of lipid research. - 0022-2275 .- 1539-7262. ; 51:1, s. 103-11
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Journal article (peer-reviewed)abstract
- Promoter polymorphisms in microsomal triglyceride transfer protein (MTTP) have been associated with decreased plasma lipids but an increased risk for ischemic heart disease (IHD), indicating that MTTP influences the susceptibility for IHD independent of plasma lipids. The objective of this study was to characterize the functional promoter polymorphism in MTTP predisposing to IHD and its underlying mechanism. Use of pyrosequencing technology revealed that presence of the minor alleles of the promoter polymorphisms -493G>T and -164T>C result in lower transcription of MTTP in vivo in the heart, liver, and macrophages. In vitro experiments indicated that the minor -164C allele mediates the lower gene expression and that C/EBP binds to the polymorphic region in an allele-specific manner. Furthermore, homozygous carriers of the -164C were found to have increased risk for IHD as shown in a case-control study including a total of 544 IHD patients and 544 healthy control subjects. We concluded that carriers of the minor -164C allele have lower expression of MTTP in the heart, mediated at least partly by the transcription factor CCAAT/enhancer binding protein, and that reduced concentration of MTTP in the myocardium may contribute to IHD upon ischemic damage.
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- Magne, J., et al.
(author)
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The minor allele of the missense polymorphism Ser251Pro in perilipin 2 (PLIN2) disrupts an alpha-helix, affects lipolysis, and is associated with reduced plasma triglyceride concentration in humans
- 2013
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In: Faseb Journal. - : Wiley. - 0892-6638 .- 1530-6860. ; 27:8, s. 3090-3099
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Journal article (peer-reviewed)abstract
- Perilipin 2 (PLIN2) is the most abundant lipid droplet (LD)-associated protein in nonadipose tissue, and its expression correlates with intracellular lipid accumulation. Here we identified a missense polymorphism, Ser251Pro, that has major effect on protein structure and function, along with an influence on human plasma triglyceride concentration. The evolutionarily conserved Ser251Pro polymorphism was identified with the ClustalW program. Structure modeling using 3D-JigSaw and the Chimera package revealed that the Pro251 allele disrupts a predicted -helix in PLIN2. Analyses of macrophages from individuals carrying Ser251Pro variants and human embryonic kidney 293 (HEK293) cells stably transfected with either of the alleles demonstrated that the Pro251 variant causes increased lipid accumulation and decreased lipolysis. Analysis of LD size distribution in stably transfected cells showed that the minor Pro251 allele resulted in an increased number of small LDs per cell and increased perilipin 3 protein expression levels as compared with cells carrying the major Ser251 allele. Genotyping of 2113 individuals indicated that the Pro251 variant is associated with decreased plasma triglyceride and very low-density lipoprotein concentrations. Altogether, these data provide the first evidence of a polymorphism in PLIN2 that affects PLIN2 function and may influence the development of metabolic and cardiovascular diseases.
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- Nguyen, H. Q., et al.
(author)
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Electrostatic control of quasiparticle poisoning in a hybrid semiconductor-superconductor island
- 2023
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In: Physical Review B. - 2469-9950. ; 108:4
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Journal article (peer-reviewed)abstract
- The performance of superconducting devices is often degraded by the uncontrolled appearance and disappearance of quasiparticles, a process known as poisoning. We demonstrate the electrostatic control of quasiparticle poisoning in the form of single-charge tunneling across a fixed barrier onto a Coulomb island in an InAs/Al hybrid nanowire. High-bandwidth charge sensing was used to monitor the charge occupancy of the island across Coulomb blockade peaks, where tunneling rates were maximal, and Coulomb valleys, where tunneling was absent. Electrostatic gates changed the on-peak tunneling rates by two orders of magnitude for a barrier with fixed normal-state resistance, which we attribute to the gate dependence of the size and softness of the induced superconducting gap on the island, corroborated by separate density-of-states measurements. Temperature and magnetic field dependence of tunneling rates are also investigated.
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- Drevinge, Christina, 1983, et al.
(author)
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Perilipin 5 is protective in the ischemic heart
- 2016
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In: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 219, s. 446-454
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Journal article (peer-reviewed)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. (C) 2016 The Authors. Published by Elsevier Ireland Ltd.
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- Klevstig, Martina, et al.
(author)
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Cardiac expression of the microsomal triglyceride transport protein protects the heart function during ischemia
- 2019
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In: Journal of Molecular and Cellular Cardiology. - : Elsevier BV. - 0022-2828 .- 1095-8584. ; 137, s. 1-8
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Journal article (peer-reviewed)abstract
- Aims: The microsomal triglyceride transport protein (MTTP) is critical for assembly and secretion of apolipoprotein B (apoB)-containing lipoproteins and is most abundant in the liver and intestine. Surprisingly, MTTP is also expressed in the heart. Here we tested the functional relevance of cardiac MTTP expression. Materials and methods: We combined clinical studies, advanced expression analysis of human heart biopsies and analyses in genetically modified mice lacking cardiac expression of the MTTP-A isoform of MTTP. Results: Our results indicate that lower cardiac MTTP expression in humans is associated with structural and perfusion abnormalities in patients with ischemic heart disease. MTTP-A deficiency in mice heart does not affect total MTTP expression, activity or lipid concentration in the heart. Despite this, MTTP-A deficient mice displayed impaired cardiac function after a myocardial infarction. Expression analysis of MTTP indicates that MTTP expression is linked to cardiac function and responses in the heart. Conclusions: Our results indicate that MTTP may play an important role for the heart function in conjunction to ischemic events.
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- Mannila, E. T., et al.
(author)
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Detecting parity effect in a superconducting device in the presence of parity switches
- 2019
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In: Physical Review B. - 2469-9950. ; 100:2
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Journal article (peer-reviewed)abstract
- We present a superconducting device showing a clear parity effect in the number of electrons, even when there is, on average, a single nonequilibrium quasiparticle present and the parity of the island switches due to quasiparticles tunneling in and out of the device at rates on the order of 100 Hz. We detect the switching by monitoring in real time the charge state of a superconducting island connected to normal leads by tunnel junctions. The quasiparticles are created by Cooper pairs breaking on the island at a rate of a few kilohertz. We demonstrate that the pair breaking is caused by the backaction of the single-electron transistor used as a charge detector. With sufficiently low probing currents, our superconducting island is free of quasiparticles 97% of the time.
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