Abstract
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.
Original language | English (US) |
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Pages (from-to) | 2535-2543 |
Number of pages | 9 |
Journal | Arteriosclerosis, thrombosis, and vascular biology |
Volume | 30 |
Issue number | 12 |
DOIs | |
State | Published - Dec 2010 |
Keywords
- circadian rhythm
- extracellular matrix
- matrix
- metalloproteinases
- peripheral arterial disease
- prostaglandins
- vascular biology
- vascular stiffness
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine