Plasma and vessel wall lipoprotein lipase have different roles in atherosclerosis

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dc.contributor.authorClee, S M
dc.contributor.authorBissada, N
dc.contributor.authorMiao, F
dc.contributor.authorMiao, L
dc.contributor.authorMarais, A D
dc.contributor.authorHenderson, H E
dc.contributor.authorSteures, P
dc.contributor.authorMcManus, J
dc.contributor.authorMcManus, B
dc.contributor.authorLeBoeuf, R C
dc.contributor.authorKastelein, J J
dc.contributor.authorHayden, M R
dc.date.accessioned2021-10-08T07:22:53Z
dc.date.available2021-10-08T07:22:53Z
dc.date.issued2000
dc.description.abstractLipoprotein lipase (LPL) is a key enzyme in lipoprotein metabolism, and has been hypothesized to exert either pro- or anti-atherogenic effects, depending on its localization. Decreased plasma LPL activity is associated with the high triglyceride (TG);-low HDL phenotype that is often observed in patients with premature vascular disease. In contrast, in the vessel wall, decreased LPL may be associated with less lipoprotein retention due to many potential mechanisms and, therefore, decreased foam cell formation. To directly assess this hypothesis, we have distinguished between the effects of variations in plasma and/or vessel wall LPL on atherosclerosis susceptibility in apoE-deficient mice. Reduced LPL in both plasma and vessel wall (LPL(+/-)E(-/-)) was associated with increased TG and increased total cholesterol (TC) compared with LPL(+/+)E(-/-) sibs. However despite their dyslipidemia, LPL(+/-)E(-/-) mice had significantly reduced lesion areas compared to the LPL(+/+)E(-/-) mice. Thus, decreased vessel wall LPL was associated with decreased lesion formation even in the presence of reduced plasma LPL activity. In contrast, transgenic mice with increased plasma LPL but with no increase in LPL expression in macrophages, and thus the vessel wall, had decreased TG and TC and significantly decreased lesion areas compared with LPL(+/+)E(-/-) mice. This demonstrates that increased plasma LPL activity alone, in the absence of an increase in vessel wall LPL, is associated with reduced susceptibility to atherosclerosis. Taken together, these results provide in vivo evidence that the contribution of LPL to atherogenesis is significantly influenced by the balance between vessel wall protein (pro-atherogenic) and plasma activity (anti-atherogenic)
dc.identifier.apacitationClee, S. M., Bissada, N., Miao, F., Miao, L., Marais, A. D., Henderson, H. E., ... Hayden, M. R. (2000). Plasma and vessel wall lipoprotein lipase have different roles in atherosclerosis. <i>The Journal of Lipid Research</i>, 41(4), 521 - 531. http://hdl.handle.net/11427/35019en_ZA
dc.identifier.chicagocitationClee, S M, N Bissada, F Miao, L Miao, A D Marais, H E Henderson, P Steures, et al "Plasma and vessel wall lipoprotein lipase have different roles in atherosclerosis." <i>The Journal of Lipid Research</i> 41, 4. (2000): 521 - 531. http://hdl.handle.net/11427/35019en_ZA
dc.identifier.citationClee, S.M., Bissada, N., Miao, F., Miao, L., Marais, A.D., Henderson, H.E., Steures, P. & McManus, J. et al. 2000. Plasma and vessel wall lipoprotein lipase have different roles in atherosclerosis. <i>The Journal of Lipid Research.</i> 41(4):521 - 531. http://hdl.handle.net/11427/35019en_ZA
dc.identifier.issn0022-2275
dc.identifier.issn1539-7262
dc.identifier.ris TY - Journal Article AU - Clee, S M AU - Bissada, N AU - Miao, F AU - Miao, L AU - Marais, A D AU - Henderson, H E AU - Steures, P AU - McManus, J AU - McManus, B AU - LeBoeuf, R C AU - Kastelein, J J AU - Hayden, M R AB - Lipoprotein lipase (LPL) is a key enzyme in lipoprotein metabolism, and has been hypothesized to exert either pro- or anti-atherogenic effects, depending on its localization. Decreased plasma LPL activity is associated with the high triglyceride (TG);-low HDL phenotype that is often observed in patients with premature vascular disease. In contrast, in the vessel wall, decreased LPL may be associated with less lipoprotein retention due to many potential mechanisms and, therefore, decreased foam cell formation. To directly assess this hypothesis, we have distinguished between the effects of variations in plasma and/or vessel wall LPL on atherosclerosis susceptibility in apoE-deficient mice. Reduced LPL in both plasma and vessel wall (LPL(+/-)E(-/-)) was associated with increased TG and increased total cholesterol (TC) compared with LPL(+/+)E(-/-) sibs. However despite their dyslipidemia, LPL(+/-)E(-/-) mice had significantly reduced lesion areas compared to the LPL(+/+)E(-/-) mice. Thus, decreased vessel wall LPL was associated with decreased lesion formation even in the presence of reduced plasma LPL activity. In contrast, transgenic mice with increased plasma LPL but with no increase in LPL expression in macrophages, and thus the vessel wall, had decreased TG and TC and significantly decreased lesion areas compared with LPL(+/+)E(-/-) mice. This demonstrates that increased plasma LPL activity alone, in the absence of an increase in vessel wall LPL, is associated with reduced susceptibility to atherosclerosis. Taken together, these results provide in vivo evidence that the contribution of LPL to atherogenesis is significantly influenced by the balance between vessel wall protein (pro-atherogenic) and plasma activity (anti-atherogenic) DA - 2000 DB - OpenUCT DP - University of Cape Town IS - 4 J1 - The Journal of Lipid Research LK - https://open.uct.ac.za PY - 2000 SM - 0022-2275 SM - 1539-7262 T1 - Plasma and vessel wall lipoprotein lipase have different roles in atherosclerosis TI - Plasma and vessel wall lipoprotein lipase have different roles in atherosclerosis UR - http://hdl.handle.net/11427/35019 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/35019
dc.identifier.vancouvercitationClee SM, Bissada N, Miao F, Miao L, Marais AD, Henderson HE, et al. Plasma and vessel wall lipoprotein lipase have different roles in atherosclerosis. The Journal of Lipid Research. 2000;41(4):521 - 531. http://hdl.handle.net/11427/35019.en_ZA
dc.language.isoeng
dc.publisher.departmentDepartment of Medicine
dc.publisher.facultyFaculty of Health Sciences
dc.sourceThe Journal of Lipid Research
dc.source.journalissue4
dc.source.journalvolume41
dc.source.pagination521 - 531
dc.source.urihttps://dx.doi.org/10.7196/sajs.718
dc.subject.otherAnimals
dc.subject.otherAorta
dc.subject.otherApolipoproteins E
dc.subject.otherArteriosclerosis
dc.subject.otherDisease Models, Animal
dc.subject.otherEndothelium, Vascular
dc.subject.otherLipoprotein Lipase
dc.subject.otherLipoproteins, HDL
dc.subject.otherMice
dc.subject.otherMice, Inbred C57BL
dc.subject.otherMice, Mutant Strains
dc.subject.otherMice, Transgenic
dc.subject.otherTriglycerides
dc.subject.otherApolipoproteins E
dc.subject.otherLipoproteins, HDL
dc.titlePlasma and vessel wall lipoprotein lipase have different roles in atherosclerosis
dc.typeJournal Article
uct.type.publicationResearch
uct.type.resourceJournal Article
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