Matrix metalloproteinase 2 and 9 dysfunction underlie vascular stiffness in circadian clock mutant mice

Ciprian B. Anea, M. Irfan Ali, Jessica M. Osmond, Jennifer C. Sullivan, David W. Stepp, Ana M. Merloiu, R. Daniel Rudic

Research output: Contribution to journalArticle

41 Scopus citations


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 languageEnglish (US)
Pages (from-to)2535-2543
Number of pages9
JournalArteriosclerosis, thrombosis, and vascular biology
Issue number12
Publication statusPublished - Dec 1 2010



  • circadian rhythm
  • extracellular matrix
  • matrix
  • metalloproteinases
  • peripheral arterial disease
  • prostaglandins
  • vascular biology
  • vascular stiffness

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this