Acute elevation of plasma PLTP activity strongly increases pre-existing atherosclerosis

Arteriosclerosis, Thrombosis, and Vascular Biology
Matthijs MoerlandRini de Crom

Abstract

A transgenic mouse model was generated that allows conditional expression of human PLTP, based on the tetracycline-responsive gene system, to study the effects of an acute increase in plasma PLTP activity as may occur in inflammation. The effects of an acute elevation of plasma PLTP activity on the metabolism of apolipoprotein B-containing lipoproteins and on diet-induced pre-existing atherosclerosis were determined in mice displaying a humanized lipoprotein profile (low-density lipoprotein receptor knockout background). Induced expression of PLTP strongly increases plasma VLDL levels in LDL receptor knockout mice, whereas VLDL secretion is not affected. The elevation in plasma triglyceride levels is explained by a PLTP-dependent inhibition of VLDL catabolism, which is caused, at least partly, by a decreased lipoprotein lipase activity. Together with the decreased plasma HDL levels, the acutely increased PLTP expression results in a highly atherogenic lipoprotein profile. Induction of PLTP expression leads to a further increase in size of pre-existing atherosclerotic lesions, even on a chow diet. In addition, the lesions contain more macrophages and less collagen relative to controls, suggesting a less stable lesion phenotype. ...Continue Reading

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Citations

Apr 18, 2013·Current Atherosclerosis Reports·Julian C van CapelleveenJohn J P Kastelein
Nov 26, 2009·The Journal of Pharmacology and Experimental Therapeutics·Yi LuoXian-Cheng Jiang
Feb 22, 2013·The Journal of Clinical Investigation·Roland KlingenbergGöran K Hansson
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Jan 22, 2011·Arteriosclerosis, Thrombosis, and Vascular Biology·David MassonLaurent Lagrost
Jul 13, 2013·Arteriosclerosis, Thrombosis, and Vascular Biology·Amirfarbod YazdanyarXian-Cheng Jiang
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Jul 9, 2008·Current Opinion in Lipidology·Adriaan G HolleboomJan Albert Kuivenhoven
Feb 15, 2019·Circulation Research·Amélie PinardDianna M Milewicz
Feb 18, 2014·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Anthony BrehmRobert Foronjy
Sep 6, 2020·Journal of Neurochemistry·Steve PedriniRalph N Martins
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Sep 8, 2009·Atherosclerosis·Eder C R Quintão, Patrícia M Cazita
Jul 9, 2011·Biochimica Et Biophysica Acta·John J AlbersMarian C Cheung

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