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| Fältnamn | Indikatorer | Metadata |
|---|---|---|
| 000 | 08462naa a2201429 4500 | |
| 001 | oai:gup.ub.gu.se/282972 | |
| 003 | SwePub | |
| 008 | 240910s2019 | |||||||||||000 ||eng| | |
| 009 | oai:prod.swepub.kib.ki.se:141456399 | |
| 009 | oai:lup.lub.lu.se:95c10b9c-1e9f-44a3-bc04-d77fe96b5c78 | |
| 024 | 7 | a https://gup.ub.gu.se/publication/2829722 URI |
| 024 | 7 | a https://doi.org/10.1111/joim.129512 DOI |
| 024 | 7 | a http://kipublications.ki.se/Default.aspx?queryparsed=id:1414563992 URI |
| 024 | 7 | a https://lup.lub.lu.se/record/95c10b9c-1e9f-44a3-bc04-d77fe96b5c782 URI |
| 040 | a (SwePub)gud (SwePub)kid (SwePub)lu | |
| 041 | a eng | |
| 042 | 9 SwePub | |
| 072 | 7 | a ref2 swepub-contenttype |
| 072 | 7 | a art2 swepub-publicationtype |
| 100 | 1 | a Saliba-Gustafsson, P.u Karolinska Institute,Karolinska Institutet,Stanford University,Karolinska University Hospital4 aut |
| 245 | 1 0 | a Subclinical atherosclerosis and its progression are modulated by PLIN2 through a feed-forward loop between LXR and autophagy |
| 264 | c 2019-07-29 | |
| 264 | 1 | b Wiley,c 2019 |
| 520 | a 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. | |
| 650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Kardiologi0 (SwePub)302062 hsv//swe |
| 650 | 7 | a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Cardiac and Cardiovascular Systems0 (SwePub)302062 hsv//eng |
| 653 | a 27OH-cholesterol | |
| 653 | a atherosclerosis | |
| 653 | a autophagy | |
| 653 | a liver-X-receptor | |
| 653 | a PLIN2 | |
| 653 | a reverse cholesterol transport | |
| 653 | a macrophage foam cells | |
| 653 | a accumulation | |
| 653 | a efflux | |
| 653 | a identification | |
| 653 | a stimulation | |
| 653 | a metabolism | |
| 653 | a receptors | |
| 653 | a ser251pro | |
| 653 | a protects | |
| 653 | a General & Internal Medicine | |
| 700 | 1 | a Pedrelli, M.u Karolinska Institute,Karolinska Institutet4 aut |
| 700 | 1 | a Gertow, K.u Karolinska Institute,Karolinska University Hospital4 aut |
| 700 | 1 | a Werngren, O.u Karolinska Institute,Karolinska University Hospital4 aut |
| 700 | 1 | a Janas, V.u Karolinska Institute,Karolinska University Hospital4 aut |
| 700 | 1 | a Pourteymour, S.4 aut |
| 700 | 1 | a Baldassarre, D.u University of Milan,Centro Cardiologico Monzino4 aut |
| 700 | 1 | a Tremoli, E.u Centro Cardiologico Monzino,University of Milan4 aut |
| 700 | 1 | a Veglia, F.u Centro Cardiologico Monzino4 aut |
| 700 | 1 | a Rauramaa, R.u University of Eastern Finland4 aut |
| 700 | 1 | a Smit, A. J.u University Medical Center Groningen4 aut |
| 700 | 1 | a Giral, P.u Pitié-Salpêtrière University Hospital4 aut |
| 700 | 1 | a Kurl, S.u University of Eastern Finland4 aut |
| 700 | 1 | a Pirro, M.u University of Perugia4 aut |
| 700 | 1 | a de Faire, U.u Karolinska Institute,Karolinska Institutet4 aut |
| 700 | 1 | a Humphries, S. E.u Karolinska Institute,Karolinska Institutet,University College London,Karolinska University Hospital4 aut |
| 700 | 1 | a Hamsten, A.u Karolinska Institute,Karolinska Institutet,Karolinska University Hospital4 aut |
| 700 | 1 | a Gonçalves, I.u Lund University,Lunds universitet,Kardiovaskulär forskning - translationella studier,Forskargrupper vid Lunds universitet,Cardiovascular Research - Translational Studies,Lund University Research Groups4 aut0 (Swepub:lu)medf-igo |
| 700 | 1 | a Orho-Melander, M.u Lund University,Lunds universitet,Diabetes - kardiovaskulär sjukdom,Forskargrupper vid Lunds universitet,Diabetes - Cardiovascular Disease,Lund University Research Groups4 aut0 (Swepub:lu)endo-mor |
| 700 | 1 | a Franco-Cereceda, A.u Karolinska Institute,Karolinska Institutet,Karolinska University Hospital4 aut |
| 700 | 1 | a Borén, Jan,d 1963u University 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 Hospital4 aut0 (Swepub:gu)xborej |
| 700 | 1 | a Eriksson, P.u Karolinska Institute,Karolinska Institutet,Karolinska University Hospital4 aut |
| 700 | 1 | a Magne, J.u Karolinska Institute,Karolinska Institutet,St Jude Children´s Research Hospital, Memphis,Karolinska University Hospital4 aut |
| 700 | 1 | a Parini, P.4 aut |
| 700 | 1 | a Ehrenborg, E.4 aut |
| 700 | 1 | a Sirtori, C. R.4 aut |
| 700 | 1 | a Castelnuovo, S.4 aut |
| 700 | 1 | a Amato, M.4 aut |
| 700 | 1 | a Frigerio, B.4 aut |
| 700 | 1 | a Ravani, A.4 aut |
| 700 | 1 | a Sansaro, D.4 aut |
| 700 | 1 | a Tedesco, C.4 aut |
| 700 | 1 | a Bovis, F.4 aut |
| 700 | 1 | a Discacciati, A.4 aut |
| 700 | 1 | a Ahl, M.4 aut |
| 700 | 1 | a Blomgren, G.4 aut |
| 700 | 1 | a Eriksson, M. J.4 aut |
| 700 | 1 | a Fahlstadius, P.4 aut |
| 700 | 1 | a Heinonen, M.4 aut |
| 700 | 1 | a Nilson, L.4 aut |
| 700 | 1 | a Cooper, J.4 aut |
| 700 | 1 | a Acharya, J.4 aut |
| 700 | 1 | a Huttunen, K.4 aut |
| 700 | 1 | a Rauramaa, E.4 aut |
| 700 | 1 | a Pekkarinen, H.4 aut |
| 700 | 1 | a Penttila, I. M.4 aut |
| 700 | 1 | a Torronen, J.4 aut |
| 700 | 1 | a van Gessel, A. I.4 aut |
| 700 | 1 | a van Roon, A. M.4 aut |
| 700 | 1 | a Teune, G. C.4 aut |
| 700 | 1 | a Kuipers, W. D.4 aut |
| 700 | 1 | a Bruin, M.4 aut |
| 700 | 1 | a Nicolai, A.4 aut |
| 700 | 1 | a Haarsma-Jorritsma, P.4 aut |
| 700 | 1 | a Mulder, D. J.4 aut |
| 700 | 1 | a Bilo, H. J. G.4 aut |
| 700 | 1 | a Smeets, G. H.4 aut |
| 700 | 1 | a Beaudeux, J. L.4 aut |
| 700 | 1 | a Kahn, J. F.4 aut |
| 700 | 1 | a Carreau, V.4 aut |
| 700 | 1 | a Kontush, A.4 aut |
| 700 | 1 | a Karppi, J.4 aut |
| 700 | 1 | a Nurmi, T.4 aut |
| 700 | 1 | a Nyyssonen, K.4 aut |
| 700 | 1 | a Salonen, R.4 aut |
| 700 | 1 | a Tuomainen, T. P.4 aut |
| 700 | 1 | a Tuomainen, J.4 aut |
| 700 | 1 | a Kauhanen, J.4 aut |
| 700 | 1 | a Vaudo, G.4 aut |
| 700 | 1 | a Alaeddin, A.4 aut |
| 700 | 1 | a Siepi, D.4 aut |
| 700 | 1 | a Lupattelli, G.4 aut |
| 700 | 1 | a Schillaci, G.4 aut |
| 710 | 2 | a Karolinska Instituteb Karolinska Institutet4 org |
| 773 | 0 | t Journal of Internal Medicined : Wileyg 286:6, s. 660-675q 286:6<660-675x 0954-6820x 1365-2796 |
| 856 | 4 | u https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/joim.12951 |
| 856 | 4 | u http://dx.doi.org/10.1111/joim.12951x freey FULLTEXT |
| 856 | 4 8 | u https://gup.ub.gu.se/publication/282972 |
| 856 | 4 8 | u https://doi.org/10.1111/joim.12951 |
| 856 | 4 8 | u http://kipublications.ki.se/Default.aspx?queryparsed=id:141456399 |
| 856 | 4 8 | u https://lup.lub.lu.se/record/95c10b9c-1e9f-44a3-bc04-d77fe96b5c78 |
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- Baldassarre, D.
- Tremoli, E.
- Veglia, F.
- Rauramaa, R.
- Smit, A. J.
- Giral, P.
- Kurl, S.
- Pirro, M.
- de Faire, U.
- Humphries, S. E.
- Hamsten, A.
- Gonçalves, I.
- Orho-Melander, M ...
- Franco-Cereceda, ...
- Borén, Jan, 1963
- Eriksson, P.
- Magne, J.
- Parini, P.
- Ehrenborg, E.
- Sirtori, C. R.
- Castelnuovo, S.
- Amato, M.
- Frigerio, B.
- Ravani, A.
- Sansaro, D.
- Tedesco, C.
- Bovis, F.
- Discacciati, A.
- Ahl, M.
- Blomgren, G.
- Eriksson, M. J.
- Fahlstadius, P.
- Heinonen, M.
- Nilson, L.
- Cooper, J.
- Acharya, J.
- Huttunen, K.
- Rauramaa, E.
- Pekkarinen, H.
- Penttila, I. M.
- Torronen, J.
- van Gessel, A. I ...
- van Roon, A. M.
- Teune, G. C.
- Kuipers, W. D.
- Bruin, M.
- Nicolai, A.
- Haarsma-Jorritsm ...
- Mulder, D. J.
- Bilo, H. J. G.
- Smeets, G. H.
- Beaudeux, J. L.
- Kahn, J. F.
- Carreau, V.
- Kontush, A.
- Karppi, J.
- Nurmi, T.
- Nyyssonen, K.
- Salonen, R.
- Tuomainen, T. P.
- Tuomainen, J.
- Kauhanen, J.
- Vaudo, G.
- Alaeddin, A.
- Siepi, D.
- Lupattelli, G.
- Schillaci, G.
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