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dc.contributor.authorYesilaltay, Ayce
dc.contributor.authorDaniels, Kathleen
dc.contributor.authorPal, Rinku
dc.contributor.authorKrieger, Monty
dc.contributor.authorKocher, Olivier
dc.date.accessioned2010-03-10T20:59:43Z
dc.date.available2010-03-10T20:59:43Z
dc.date.issued2009-12
dc.date.submitted2009-08
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/1721.1/52489
dc.description.abstractBackground: PDZK1 is a four PDZ-domain containing protein that binds to the carboxy terminus of the HDL receptor, scavenger receptor class B type I (SR-BI), and regulates its expression, localization and function in a tissue-specific manner. PDZK1 knockout (KO) mice are characterized by a marked reduction of SR-BI protein expression (~95%) in the liver (lesser or no reduction in other organs) with a concomitant 1.7 fold increase in plasma cholesterol. PDZK1 has been shown to be atheroprotective using the high fat/high cholesterol (‘Western’) diet-fed murine apolipoprotein E (apoE) KO model of atherosclerosis, presumably because of its role in promoting reverse cholesterol transport via SR-BI. Principal Findings: Here, we have examined the effects of PDZK1 deficiency in apoE KO mice fed with the atherogenic ‘Paigen’ diet for three months. Relative to apoE KO, PDZK1/apoE double KO (dKO) mice showed increased plasma lipids (33% increase in total cholesterol; 49 % increase in unesterified cholesterol; and 36% increase in phospholipids) and a 26% increase in aortic root lesions. Compared to apoE KO, dKO mice exhibited substantial occlusive coronary artery disease: 375% increase in severe occlusions. Myocardial infarctions, not observed in apoE KO mice (although occasional minimal fibrosis was noted), were seen in 7 of 8 dKO mice, resulting in 12 times greater area of fibrosis in dKO cardiac muscle. Conclusions: These results show that Paigen-diet fed PDZK1/apoE dKO mice represent a new animal model useful for studying coronary heart disease and suggest that PDZK1 may represent a valuable target for therapeutic intervention.en
dc.description.sponsorshipNational Institutes of Health (Grants HL-52212, HL66105, and HL077780)en
dc.language.isoen_US
dc.publisherPublic Library of Scienceen
dc.relation.isversionofhttp://dx.doi.org/10.1371/journal.pone.0008103en
dc.rightsCreative Commons Attributionen
dc.rights.urihttp://creativecommons.org/licenses/by/2.5/en
dc.sourcePLoSen
dc.titleLoss of PDZK1 Causes Coronary Artery Occlusion and Myocardial Infarction in Paigen Diet-Fed Apolipoprotein E Deficient Miceen
dc.typeArticleen
dc.identifier.citationYesilaltay, Ayce et al. “Loss of PDZK1 Causes Coronary Artery Occlusion and Myocardial Infarction in Paigen Diet-Fed Apolipoprotein E Deficient Mice.” PLoS ONE 4.12 (2009): e8103.en
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.approverKrieger, Monty
dc.contributor.mitauthorKrieger, Monty
dc.contributor.mitauthorYesilaltay, Ayce
dc.relation.journalPLoS ONEen
dc.eprint.versionFinal published versionen
dc.type.urihttp://purl.org/eprint/type/JournalArticleen
eprint.statushttp://purl.org/eprint/status/PeerRevieweden
dspace.orderedauthorsYesilaltay, Ayce; Daniels, Kathleen; Pal, Rinku; Krieger, Monty; Kocher, Olivieren
dc.identifier.orcidhttps://orcid.org/0000-0003-4541-5181
dc.identifier.orcidhttps://orcid.org/0000-0001-9905-5316
mit.licensePUBLISHER_CCen
mit.metadata.statusComplete


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