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, Radu Daniel Rudic

Research output: Contribution to journalArticle

39 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)2535-2543
Number of pages9
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume30
Issue number12
DOIs
StatePublished - Dec 1 2010

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Circadian Clocks
Vascular Stiffness
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Knockout Mice
Arteries
Matrix Metalloproteinases
Compliance
Blood Vessels
Pulse Wave Analysis
Elasticity
Arterioles
Extracellular Matrix
Ultrasonography

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Matrix metalloproteinase 2 and 9 dysfunction underlie vascular stiffness in circadian clock mutant mice. / Anea, Ciprian B.; Irfan Ali, M.; Osmond, Jessica M.; Sullivan, Jennifer C; Stepp, David W; Merloiu, Ana M.; Rudic, Radu Daniel.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 30, No. 12, 01.12.2010, p. 2535-2543.

Research output: Contribution to journalArticle

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AU - Rudic, Radu Daniel

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