Lymphocytes are not required for the rapid onset of coronary heart disease in scavenger receptor class B type I/apolipoprotein E double knockout mice.
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.


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.
Karackattu
Sharon L
SL
Biology Department, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Picard
Michael H
MH
Krieger
Monty
M
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D015415:Biomarkers; D003327:Coronary Disease / Q000235:genetics / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005355:Fibrosis; D007150:Immunohistochemistry; D008017:Life Expectancy; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018110:Receptors, Lipoprotein / Q000235:genetics*; D051122:Scavenger Receptors, Class B; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
D001057:Apolipoproteins E; D015415:Biomarkers; D004268:DNA-Binding Proteins; D008055:Lipids; D008074:Lipoproteins; D008565:Membrane Proteins; C499308:Rag2 protein, mouse; D018110:Receptors, Lipoprotein; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; C064655:V(D)J recombination activating protein 2