Genetic approaches to studying coronary heart disease in SR-BI/apoE double knockout mice

Coronary heart disease (CHD) is a major healthcare concern in both developed and developing nations. The principal cause of CHD is atherosclerosis, the buildup of fatty deposits in vessel walls. SR-BI/apoE double knockout (dKO) mice are a novel mouse model of human CHD, exhibiting spontaneous coronary occlusive atherosclerosis, myocardial infarction, cardiac dysfunction and premature death. This model represents a unique system in which to study the two principal underlying mechanisms of atherosclerosis and CHD, inflammation and lipoprotein lipid metabolism. The first part of this thesis demonstrates that B- and T-lymphocytes do not play a significant role in development or progression of atherosclerosis or CHD in SR-BI/apoE dKO mice. More importantly, this study eliminates B- and T-lymphocyte-driven immunoglobulin-mediated inflammation as a significant mechanism instigating or exacerbating myocardial injury in dKO mice. Strikingly, the mice generated for this study also demonstrate that genetic background influences both average lifespan and lifespan variability of dKO mice. The second study investigates alterations in lipoprotein metabolism on CHD and demonstrates that hepatic lipase deficiency, despite raising plasma cholesterol levels, retards development of both aortic and coronary occlusive atherosclerosis in dKO mice.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Biology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2006

Author dc:creator

• Karackattu, Sharon Liz

Advisor dc:contributor.advisor

• Monty Krieger.

• Biology.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/34279
• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Identifier URI

http://dspace.mit.edu/handle/1721.1/34279

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/34279