Objective- To determine if elasticity in blood vessels is compromised in circadian clock-mutant mice (Bmal1-knockout [KO] and Per-triple KO) and if matrix metalloproteinases (MMPs) might confer these changes in compliance. Methods and Results- High-resolution ultrasonography in vivo revealed impaired remodeling and increased pulse-wave velocity in the arteries of Bmal1-KO and Per-triple KO mice. In addition, compliance of remodeled arteries and naïve pressurized arterioles ex vivo from Bmal1-KO and Per-triple KO mice was reduced, consistent with stiffening of the vascular bed. The observed vascular stiffness was coincident with dysregulation of MMP-2 and MMP-9 in Bmal1-KO mice. Furthermore, inhibition of MMPs improved indexes of pathological remodeling in wild-type mice, but the effect was abolished in Bmal1-KO mice. Conclusion- Circadian clock dysfunction contributes to hardening of arteries, which may involve impaired control of the extracellular matrix composition. © 2010 American Heart Association. All rights reserved.
CITATION STYLE
Anea, C. B., Irfan Ali, M., Osmond, J. M., Sullivan, J. C., Stepp, D. W., Merloiu, A. M., & Rudic, R. D. (2010). Matrix metalloproteinase 2 and 9 dysfunction underlie vascular stiffness in circadian clock mutant mice. Arteriosclerosis, Thrombosis, and Vascular Biology, 30(12), 2535–2543. https://doi.org/10.1161/ATVBAHA.110.214379
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