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Pathological vascular stiffness in mice with disrupted circadian rhythm
Author(s) -
Anea Ciprian,
Ali Mohammed Irfan,
Osmond Jessica,
Stepp David W.,
Rudic Dan
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.802.4
Subject(s) - circadian rhythm , extracellular matrix , endocrinology , medicine , arterial stiffness , artery , femoral artery , compliance (psychology) , matrix metalloproteinase , cardiology , biology , microbiology and biotechnology , psychology , social psychology , blood pressure
The transcription factor Bmal1 is an integral component of the molecular machinery that drives circadian rhythm. Previously, we have described that mice with disruption of Bmal1 (Bmal1‐KO) exhibit pathological remodeling and enhanced vascular injury. Herein, we undertook studies to examine both large artery and resistance artery compliance in these mice with dysfunctional circadian clocks. After inducing arterial remodeling by ligation of the common carotid artery, high resolution ultrasound imaging was implemented in vivo in live, anesthetized mice, to reveal dilatation, impaired remodeling, and increased vascular stiffness in the arteries undergoing remodeling of Bmal1‐KO mice. Furthermore, vascular compliance of naïve, unligated resistance vessels (third order branches of the femoral artery) was reduced in Bmal1‐KO mice. As matrix metalloproteinases (MMPs) represent key elements involved in the turnover of the extracellular matrix and vascular stiffness, we assessed MMP activity and expression in arteries of Bmal1‐KO mice. Bmal1‐KO mice exhibited an increase in MMP activity and expression in naïve vessels, an effect which was further exacerbated in remodeled vessels. These data suggest that circadian clock regulation of extracellular matrix turnover may be an important factor in the progression to hardening of arteries during vascular disease.