Abstract 402: Calpain-1 Deficiency Does Not Affect Angiotensin II-Induced Atherosclerosis or Abdominal Aortic Aneurysms in Male LDL Receptor--Deficient Mice
Background and Objective: Chronic infusion of angiotensin II (AngII) augments the development of atherosclerosis and induces abdominal aortic aneurysms (AAAs) in hypercholesterolemic mice. Recently, we demonstrated that pharmacological inhibition of calpains, a class of calcium-activated, neutral cysteine proteases, attenuated AngII-induced atherosclerosis and AAAs in mice. The purpose of this study was to determine the contribution of calpain-1 in the development of AngII-induced atherosclerosis and AAA using genetically modified mice.
Methods and Results: Male LDL receptor -/- mice (10-12 weeks old) that were either calpain-1 +/+ or -/- (n=20 per group) were fed a saturated fat-enriched diet (21% wt/wt milk fat; 0.15% wt/wt cholesterol) for 5 weeks. After 1 week of feeding a saturated fat enriched diet, mice were infused subcutaneously with AngII (1,000 ng/kg/min) by osmotic minipumps for 4 weeks. AngII increased systolic blood pressure similarly in both groups (pre-infusion- calpain-1 +/+: 122 ± 4; calpain-1 -/-: 123 ± 6 mmHg; post-infusion calpain-1 +/+: 156 ± 5; calpain-1 -/-: 153 ± 6 mmHg). Deficiency of calpain-1 had no effect on plasma cholesterol concentrations (calpain-1 +/+: 1589 ± 39; calpain-1 -/-: 1531 ± 70 mg/dL) or lipoprotein-cholesterol distributions during AngII infusion. AngII infusion led to development of AAA formation in 76% of calpain-1 +/+ mice and 65% in calpain-1 -/- mice. This difference was not statistically significant. AngII infusion greatly augmented the development of aortic arch atherosclerosis that was not attenuated in calpain-1 -/- mice, (calpain-1 +/+: 6.9 ± 1.0 %; calpain-1 -/- : 5.1 ± 0.8 % of arch area intimal lesions; P = not significant).
Conclusion: These findings suggest that calpain-1 does not contribute to the development of angiotensin II-induced atherosclerosis or AAAs.
- © 2012 by American Heart Association, Inc.