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Role of ANGPTL-4 in the regulation of the functional pool of LPL in mouse heart
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
2017 (English)Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
Abstract [en]

The heart is constantly pumping blood through the body to provide tissues with oxygen and nutrients and retrieve waste products. The cardiomyocytes therefore have a high energy demand. The mostly used energy substrate is fatty acids, covering approximately 70 % of the energy need under normal conditions. Fatty acids reach the heart either bound to albumin or delivered from circulating lipoproteins after liberation from triglycerides through the action of the enzyme lipoprotein lipase (LPL). LPL is produced in parenchymal cells like cardiomyocytes and is then transported to the luminal side of capillary endothelium where it hydrolyses lipoproteins. The LPL activity is rapidly modulated according to the needs of the tissue and the regulation occurs mostly by post-translational mechanisms. Derangements in the normal function of the LPL system of the heart have implications for ischemia, diabetic myopathy and other forms of heart failure.

One candidate protein that regulates LPL activity in other tissues is angiopoietin-like protein 4 (ANGPTL-4). Binding of this protein to the active LPL dimer causes dissociation to inactive LPL monomers. In mice, the expression of Angptl4 is seen in liver and adipose tissue, but also in skeletal muscle and heart.

The aim of this study was to identify the role of ANGPTL-4 for control of LPL on the cardiac capillary endothelium in mice. This pool of functional LPL in the heart can only be studied by extracorporal retrograde perfusion of the coronary arteries by heparin in order to release the LPL that is bound to the endothelium. Hearts from mice with knock-out or transgenic overexpression of Angptl4 was perfused, and the LPL activity was determined in perfusates from fasted and fed mice. In the Angptl4 knock-out mice, the nutritional regulation of the amount of LPL activity on the endothelium was intact, but acted from a higher baseline level. In the transgenic mice the LPL activity was pressed down to a low level in both fed and fasted mice, and the typical nutritional regulation of LPL activity was wiped out. The large pressure on the LPL system by the elevated amounts of ANGPTL-4 had disabled the regulatory system.

In conclusion, ANGPTL-4 seems to be responsible for control of the baseline level of LPL activity on the endothelium of mouse hearts. Other factors than ANGPTL-4 must, however, be responsible for the normal, rapid modulation of LPL activity according to the nutritional requirement of the tissue.

Place, publisher, year, edition, pages
2017. , p. 13
National Category
Microbiology in the medical area
Identifiers
URN: urn:nbn:se:umu:diva-144150OAI: oai:DiVA.org:umu-144150DiVA, id: diva2:1176852
Educational program
Medical Programme
Supervisors
Examiners
Available from: 2018-06-25 Created: 2018-01-23 Last updated: 2018-06-25Bibliographically approved

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