PMID- 20362292 OWN - NLM STAT- MEDLINE DCOM- 20101206 LR - 20220321 IS - 1879-1484 (Electronic) IS - 0021-9150 (Print) IS - 0021-9150 (Linking) VI - 211 IP - 2 DP - 2010 Aug TI - Total lymphocyte deficiency attenuates AngII-induced atherosclerosis in males but not abdominal aortic aneurysms in apoE deficient mice. PG - 399-403 LID - 10.1016/j.atherosclerosis.2010.02.034 [doi] AB - 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. METHODS AND 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. CONCLUSION: T and B lymphocyte deficiency attenuates AngII-induced atherosclerosis in males but not AAA formation in apoE -/- mice. CI - Copyright 2010 Elsevier Ireland Ltd. All rights reserved. FAU - Uchida, Haruhito A AU - Uchida HA AD - Saha Cardiovascular Research Center, University of Kentucky, Lexington, KY 40536, USA. FAU - Kristo, Fjoralba AU - Kristo F FAU - Rateri, Debra L AU - Rateri DL FAU - Lu, Hong AU - Lu H FAU - Charnigo, Richard AU - Charnigo R FAU - Cassis, Lisa A AU - Cassis LA FAU - Daugherty, Alan AU - Daugherty A LA - eng GR - P01 HL080100/HL/NHLBI NIH HHS/United States GR - P01 HL080100-02/HL/NHLBI NIH HHS/United States GR - P01 HL80100/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20100304 PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Apolipoproteins E) RN - 11128-99-7 (Angiotensin II) SB - IM MH - Aneurysm/genetics/pathology MH - Angiotensin II/*genetics MH - Animals MH - Aortic Aneurysm, Abdominal/*genetics MH - Apolipoproteins E/*genetics MH - Atherosclerosis/*genetics MH - B-Lymphocytes/cytology MH - Female MH - *Gene Expression Regulation MH - Genotype MH - Hypercholesterolemia/genetics MH - Lymphocytes/*cytology MH - Male MH - Mice MH - T-Lymphocytes/cytology PMC - PMC2900415 MID - NIHMS185431 EDAT- 2010/04/07 06:00 MHDA- 2010/12/14 06:00 PMCR- 2011/08/01 CRDT- 2010/04/06 06:00 PHST- 2009/06/04 00:00 [received] PHST- 2010/02/19 00:00 [revised] PHST- 2010/02/24 00:00 [accepted] PHST- 2010/04/06 06:00 [entrez] PHST- 2010/04/07 06:00 [pubmed] PHST- 2010/12/14 06:00 [medline] PHST- 2011/08/01 00:00 [pmc-release] AID - S0021-9150(10)00175-9 [pii] AID - 10.1016/j.atherosclerosis.2010.02.034 [doi] PST - ppublish SO - Atherosclerosis. 2010 Aug;211(2):399-403. doi: 10.1016/j.atherosclerosis.2010.02.034. Epub 2010 Mar 4.