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Subclinical atheros...
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Saliba-Gustafsson, P.Karolinska Institute,Karolinska Institutet,Stanford University,Karolinska University Hospital
(author)
Subclinical atherosclerosis and its progression are modulated by PLIN2 through a feed-forward loop between LXR and autophagy
- Article/chapterEnglish2019
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LIBRIS-ID:oai:gup.ub.gu.se/282972
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https://gup.ub.gu.se/publication/282972URI
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https://doi.org/10.1111/joim.12951DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:141456399URI
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https://lup.lub.lu.se/record/95c10b9c-1e9f-44a3-bc04-d77fe96b5c78URI
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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Background Hyperlipidaemia is a major risk factor for cardiovascular disease, and atherosclerosis is the underlying cause of both myocardial infarction and stroke. We have previously shown that the Pro251 variant of perilipin-2 reduces plasma triglycerides and may therefore be beneficial to reduce atherosclerosis development. Objective We sought to delineate putative beneficial effects of the Pro251 variant of perlipin-2 on subclinical atherosclerosis and the mechanism by which it acts. Methods A pan-European cohort of high-risk individuals where carotid intima-media thickness has been assessed was adopted. Human primary monocyte-derived macrophages were prepared from whole blood from individuals recruited by perilipin-2 genotype or from buffy coats from the Karolinska University hospital blood central. Results The Pro251 variant of perilipin-2 is associated with decreased intima-media thickness at baseline and over 30 months of follow-up. Using human primary monocyte-derived macrophages from carriers of the beneficial Pro251 variant, we show that this variant increases autophagy activity, cholesterol efflux and a controlled inflammatory response. Through extensive mechanistic studies, we demonstrate that increase in autophagy activity is accompanied with an increase in liver-X-receptor (LXR) activity and that LXR and autophagy reciprocally activate each other in a feed-forward loop, regulated by CYP27A1 and 27OH-cholesterol. Conclusions For the first time, we show that perilipin-2 affects susceptibility to human atherosclerosis through activation of autophagy and stimulation of cholesterol efflux. We demonstrate that perilipin-2 modulates levels of the LXR ligand 27OH-cholesterol and initiates a feed-forward loop where LXR and autophagy reciprocally activate each other; the mechanism by which perilipin-2 exerts its beneficial effects on subclinical atherosclerosis.
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Pedrelli, M.Karolinska Institute,Karolinska Institutet
(author)
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Gertow, K.Karolinska Institute,Karolinska University Hospital
(author)
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Werngren, O.Karolinska Institute,Karolinska University Hospital
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Janas, V.Karolinska Institute,Karolinska University Hospital
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Pourteymour, S.
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Baldassarre, D.Centro Cardiologico Monzino,University of Milan
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Tremoli, E.Centro Cardiologico Monzino,University of Milan
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Veglia, F.Centro Cardiologico Monzino
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Rauramaa, R.University of Eastern Finland
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Smit, A. J.University Medical Center Groningen
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Giral, P.Pitié-Salpêtrière University Hospital
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Kurl, S.University of Eastern Finland
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Pirro, M.University of Perugia
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de Faire, U.Karolinska Institute,Karolinska Institutet
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Humphries, S. E.Karolinska Institute,Karolinska Institutet,University College London,Karolinska University Hospital
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Hamsten, A.Karolinska Institute,Karolinska Institutet,Karolinska University Hospital
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Gonçalves, I.Lund University,Lunds universitet,Kardiovaskulär forskning - translationella studier,Forskargrupper vid Lunds universitet,Cardiovascular Research - Translational Studies,Lund University Research Groups(Swepub:lu)medf-igo
(author)
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Orho-Melander, M.Lund University,Lunds universitet,Diabetes - kardiovaskulär sjukdom,Forskargrupper vid Lunds universitet,Diabetes - Cardiovascular Disease,Lund University Research Groups(Swepub:lu)endo-mor
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Franco-Cereceda, A.Karolinska Institute,Karolinska Institutet,Karolinska University Hospital
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Borén, Jan,1963University of Gothenburg,Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory,Sahlgrenska University Hospital(Swepub:gu)xborej
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Eriksson, P.Karolinska Institute,Karolinska Institutet,Karolinska University Hospital
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Magne, J.Karolinska Institute,Karolinska Institutet,St Jude Children´s Research Hospital, Memphis,Karolinska University Hospital
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Parini, P.
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Ehrenborg, E.
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Sirtori, C. R.
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Castelnuovo, S.
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Amato, M.
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Frigerio, B.
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Ravani, A.
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Sansaro, D.
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Tedesco, C.
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Bovis, F.
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Discacciati, A.
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Ahl, M.
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Blomgren, G.
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Eriksson, M. J.
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Fahlstadius, P.
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Heinonen, M.
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Nilson, L.
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Cooper, J.
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Acharya, J.
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Huttunen, K.
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Rauramaa, E.
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Pekkarinen, H.
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Penttila, I. M.
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Torronen, J.
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van Gessel, A. I.
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van Roon, A. M.
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Teune, G. C.
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Kuipers, W. D.
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Bruin, M.
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Nicolai, A.
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Haarsma-Jorritsma, P.
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Mulder, D. J.
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Bilo, H. J. G.
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Smeets, G. H.
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Beaudeux, J. L.
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Kahn, J. F.
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Carreau, V.
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Kontush, A.
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Karppi, J.
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Nurmi, T.
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Nyyssonen, K.
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Salonen, R.
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Tuomainen, T. P.
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Tuomainen, J.
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Kauhanen, J.
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Vaudo, G.
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Alaeddin, A.
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Siepi, D.
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Lupattelli, G.
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Schillaci, G.
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Karolinska InstituteKarolinska Institutet
(creator_code:org_t)
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In:Journal of Internal Medicine: Wiley286:6, s. 660-6750954-68201365-2796
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Saliba-Gustafsso ...
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Pedrelli, M.
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Gertow, K.
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Werngren, O.
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Janas, V.
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Pourteymour, S.
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show more...
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Baldassarre, D.
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Tremoli, E.
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Veglia, F.
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Rauramaa, R.
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Smit, A. J.
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Giral, P.
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Kurl, S.
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Pirro, M.
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de Faire, U.
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Humphries, S. E.
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Hamsten, A.
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Gonçalves, I.
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Orho-Melander, M ...
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Franco-Cereceda, ...
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Borén, Jan, 1963
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Eriksson, P.
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Magne, J.
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Parini, P.
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Ehrenborg, E.
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Sirtori, C. R.
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Castelnuovo, S.
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Amato, M.
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Frigerio, B.
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Ravani, A.
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Sansaro, D.
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Tedesco, C.
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Bovis, F.
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Discacciati, A.
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Ahl, M.
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Blomgren, G.
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Eriksson, M. J.
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Fahlstadius, P.
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Heinonen, M.
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Nilson, L.
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Cooper, J.
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Acharya, J.
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Huttunen, K.
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Rauramaa, E.
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Pekkarinen, H.
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Penttila, I. M.
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Torronen, J.
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van Gessel, A. I ...
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van Roon, A. M.
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Teune, G. C.
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Kuipers, W. D.
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Bruin, M.
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Nicolai, A.
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Haarsma-Jorritsm ...
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Mulder, D. J.
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Bilo, H. J. G.
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Smeets, G. H.
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Beaudeux, J. L.
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Kahn, J. F.
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Carreau, V.
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Kontush, A.
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Karppi, J.
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Nurmi, T.
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Nyyssonen, K.
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Salonen, R.
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Tuomainen, T. P.
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Tuomainen, J.
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Kauhanen, J.
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Vaudo, G.
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Alaeddin, A.
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Siepi, D.
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Lupattelli, G.
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Schillaci, G.
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cardiac and Card ...
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Journal of Inter ...
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University of Gothenburg
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Karolinska Institutet
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Lund University