Published online before print February 3, 2005, doi: 10.1161/01.ATV.0000158310.64498.ac
© 2005 American Heart Association, Inc.
Atherosclerosis & Lipoproteins |
Lymphocytes Are Not Required for the Rapid Onset of Coronary Heart Disease in Scavenger Receptor Class B Type I/Apolipoprotein E Double Knockout Mice
From the Department of Biology (S.L.K., M.K.), Massachusetts Institute of Technology, Cambridge; and Division of Cardiology Department of Medicine (M.H.P.), Massachusetts General Hospital and Harvard Medical School, Boston, Mass.
Correspondence to Monty Krieger, Room 68-483, Biology Department, Massachusetts Institute of Technology, Cambridge, MA 02139. E-mail krieger{at}mit.edu
Objective— Scavenger receptor class B type I (SR-BI)/apolipoprotein E (apoE) double knockout (dKO) mice exhibit many features of human coronary heart disease (CHD), including occlusive coronary atherosclerosis, cardiac hypertrophy, myocardial infarctions, and premature death. Here we determined the influence of B and T lymphocytes, which can contribute to atherosclerosis, ischemia–reperfusion injury, and cardiomyocyte death, on pathology in dKO mice.
Method and Results— The lymphocyte-deficient SR-BI/apoE/recombination activating gene 2 (RAG2) triple knockout mice and corresponding dKO controls generated for this study exhibited essentially identical lipid-rich coronary occlusions, myocardial infarctions, cardiac dysfunction, and premature death (average lifespans 41.6±0.6 and 42.0±0.5 days, respectively).
Conclusions— B and T lymphocytes and associated immunoglobulin-mediated inflammation are not essential for the development and progression of CHD in dKO mice. Strikingly, the dKO mice bred for this study (mixed C57BL/6xSV129xBALB/c background; strain 2) compared with the previously described dKO mice (75:25 C57BL/6:SV129 background; strain 1) had a shorter mean lifespan and steeper survival curve, characteristics especially attractive for studying the effects of environmental, pharmacological, and genetic manipulations on cardiac pathophysiology.
SR-BI/apoE double knockout mice exhibit occlusive atherosclerotic coronary heart disease (CHD) characterized by myocardial infarctions, cardiac dysfunction, and premature death. Analysis of B-cell– and T-cell–deficient SR-BI/apoE/RAG2 triple knockout mice established that B and T lymphocytes do not play a key role in the pathophysiology of this model of human disease.
Key Words: atherosclerosis • HDL receptor • myocardial infarction • RAG2 • echocardiography
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