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 Nicolas | |
dc.date.accessioned | 2012-03-23T15:35:42Z | |
dc.date.issued | 2009 | |
dc.identifier.citation | Yesilaltay, Ayce, Kathleen Daniels, Rinku Pal, Monty Krieger, and Olivier Kocher. 2009. Loss of PDZK1 Causes Coronary Artery Occlusion and Myocardial Infarction in Paigen Diet-Fed Apolipoprotein E Deficient Mice. PLoS ONE 4(12): e8103. | en_US |
dc.identifier.issn | 1932-6203 | en_US |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:8438179 | |
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_US |
dc.language.iso | en_US | en_US |
dc.publisher | Public Library of Science | en_US |
dc.relation.isversionof | doi:10.1371/journal.pone.0008103 | en_US |
dc.relation.hasversion | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2779610/pdf/ | en_US |
dash.license | LAA | |
dc.subject | cardiovascular disorders | en_US |
dc.subject | coronary artery disease | en_US |
dc.subject | myocardial infarction | en_US |
dc.subject | vascular biology | en_US |
dc.title | Loss of PDZK1 Causes Coronary Artery Occlusion and Myocardial Infarction in Paigen Diet-Fed Apolipoprotein E Deficient Mice | en_US |
dc.type | Journal Article | en_US |
dc.description.version | Version of Record | en_US |
dc.relation.journal | PLoS ONE | en_US |
dash.depositing.author | Kocher, Olivier Nicolas | |
dc.date.available | 2012-03-23T15:35:42Z | |
dash.affiliation.other | HMS^Pathology | en_US |
dc.identifier.doi | 10.1371/journal.pone.0008103 | * |
dash.contributor.affiliated | Kocher, Olivier | |