Total lymphocyte deficiency attenuates AngII-induced atherosclerosis in males but not abdominal aortic aneurysms in apoE deficient mice

Abstract

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.

Figure 1. Total lymphocyte deficiency had no significant effect on basal or AngII-induced systolic blood pressure

Systolic blood pressure was determined from the mean of measurements for 5 consecutive days prior to and the last week during AngII infusion in male (A) and female groups (B). Histobars represent means and bars are SEMs. Statistical analyses were performed by ANOVA with repeated measures.

Figure 2. Total lymphocyte deficiency reduced AngII-induced atherosclerosis in male mice

The percent area of grossly discernable atherosclerotic lesions was measured in the arch and thoracic regions of aortas recovered from apoE −/− mice that are either Rag-1 +/− or −/− in male (A) and female groups (B). The area for each individual mouse is represented by circle or inverted triangle; diamonds represent means and bars represent SEMs. Statistical analyses were performed by Kruskal Wallis with follow up Z test.

Figure 3. Total lymphocyte deficiency had no significant effect on the size and incidence of AngII-induced AAAs

Size was measured as maximal diameter of suprarenal aortas in male (A) and female mice (B). The diameter for each individual mouse is represented by circle or inverted triangle; diamonds represent means, and bars are SEMs. Statistical analyses were performed by Kruskal Wallis with follow up Z test.