Total lymphocyte deficiency attenuates AngII-induced atherosclerosis in males but not abdominal aortic aneurysms in apoE deficient mice.
OBJECTIVE
T and B lymphocytes are associated with atherosclerosis and aneurysms. Angiotensin II (AngII) infusion into hypercholesterolemic mice results in augmentation of atherosclerosis and abdominal aortic aneurysm (AAA) formation. In this study, we determined whether total lymphocyte deficiency reduced AngII-induced vascular diseases.


RESULTS
ApoE deficient (apoE -/-) mice were cross-bred with recombination activating gene-1 (Rag-1) deficient mice that lack mature T and B lymphocytes. Heterozygous littermates (Rag-1 +/-) have normal lymphocytic function and served as controls. Male and female apoE -/- mice that were either Rag-1 +/- or -/- were fed a normal laboratory diet and infused with either saline or AngII (1000ng/kg/min) subcutaneously via osmotic mini pump for 28 days. Total lymphocyte deficiency had no significant effect on body weight and systolic blood pressure prior to and during AngII infusion. However, it was associated with decreased serum cholesterol concentrations. AngII infusion increased atherosclerotic lesion area in Rag-1 +/- mice compared to saline (P=0.017 in males and P=0.004 in females). This effect was significantly blunted in Rag-1 -/- male (P=0.044), but not female mice. AngII-infusion promoted increased width of the abdominal aorta, with a greater effect in males. Despite the reduction in atherosclerosis in males, Rag-1 deficiency had no significant effect on AngII-induced aortic dilation in either gender.


CONCLUSIONS
T and B lymphocyte deficiency attenuates AngII-induced atherosclerosis in males but not AAA formation in apoE -/- mice.
Uchida
Haruhito A
HA
Saha Cardiovascular Research Center, University of Kentucky, Lexington, KY 40536, USA.
Kristo
Fjoralba
F
Rateri
Debra L
DL
Lu
Hong
H
Charnigo
Richard
R
Cassis
Lisa A
LA
Daugherty
Alan
A
D000783:Aneurysm / Q000235:genetics / Q000473:pathology; D000804:Angiotensin II / Q000235:genetics*; D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000235:genetics*; D001402:B-Lymphocytes / Q000166:cytology; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D006937:Hypercholesterolemia / Q000235:genetics; D008214:Lymphocytes / Q000166:cytology*; D008297:Male; D051379:Mice; D013601:T-Lymphocytes / Q000166:cytology
D001057:Apolipoproteins E; D000804:Angiotensin II