dc.contributor.author | Yesilaltay, Ayce | |
dc.contributor.author | Daniels, Kathleen | |
dc.contributor.author | Pal, Rinku | |
dc.contributor.author | Krieger, Monty | |
dc.contributor.author | Kocher, Olivier | |
dc.date.accessioned | 2010-03-10T20:59:43Z | |
dc.date.available | 2010-03-10T20:59:43Z | |
dc.date.issued | 2009-12 | |
dc.date.submitted | 2009-08 | |
dc.identifier.issn | 1932-6203 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/52489 | |
dc.description.abstract | Background: 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.sponsorship | National Institutes of Health (Grants HL-52212, HL66105, and HL077780) | en |
dc.language.iso | en_US | |
dc.publisher | Public Library of Science | en |
dc.relation.isversionof | http://dx.doi.org/10.1371/journal.pone.0008103 | en |
dc.rights | Creative Commons Attribution | en |
dc.rights.uri | http://creativecommons.org/licenses/by/2.5/ | en |
dc.source | PLoS | en |
dc.title | Loss of PDZK1 Causes Coronary Artery Occlusion and Myocardial Infarction in Paigen Diet-Fed Apolipoprotein E Deficient Mice | en |
dc.type | Article | en |
dc.identifier.citation | Yesilaltay, 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.department | Massachusetts Institute of Technology. Department of Biology | en_US |
dc.contributor.approver | Krieger, Monty | |
dc.contributor.mitauthor | Krieger, Monty | |
dc.contributor.mitauthor | Yesilaltay, Ayce | |
dc.relation.journal | PLoS ONE | en |
dc.eprint.version | Final published version | en |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en |
dspace.orderedauthors | Yesilaltay, Ayce; Daniels, Kathleen; Pal, Rinku; Krieger, Monty; Kocher, Olivier | en |
dc.identifier.orcid | https://orcid.org/0000-0003-4541-5181 | |
dc.identifier.orcid | https://orcid.org/0000-0001-9905-5316 | |
mit.license | PUBLISHER_CC | en |
mit.metadata.status | Complete | |