Matrix metalloproteinase 2 and 9 dysfunction underlie vascular stiffness in circadian clock mutant mice
CB Anea, MI Ali, JM Osmond, JC Sullivan… - … , and vascular biology, 2010 - Am Heart Assoc
Arteriosclerosis, thrombosis, and vascular biology, 2010•Am Heart Assoc
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 …
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 …
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.
Am Heart Assoc