batimastat and Carotid-Artery-Diseases

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.. 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.. Circadian clock dysfunction contributes to hardening of arteries, which may involve impaired control of the extracellular matrix composition.

Topics: Animals; ARNTL Transcription Factors; Blood Pressure; Carotid Arteries; Carotid Artery Diseases; Cells, Cultured; Circadian Clocks; Elasticity; Endothelial Cells; Extracellular Matrix; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Mice; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Knockout; Mice, Mutant Strains; Myocytes, Smooth Muscle; Period Circadian Proteins; Phenylalanine; Protease Inhibitors; Thiophenes; Time Factors; Ultrasonography, Doppler, Pulsed