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Pathological vascular remodeling in mice with disrupted circadian rhythm
Author(s) -
Anea Ciprian Bogdan,
Sullivan Jeniffer,
Rudic Radu Daniel
Publication year - 2009
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.23.1_supplement.1033.3
Subject(s) - circadian rhythm , lumen (anatomy) , medicine , ligation , clock , circadian clock , common carotid artery , endocrinology , cardiology , biology , carotid arteries
The transcription factors Bmal1 and Clock are integral components of the molecular machinery that drive circadian rhythm. Herein, we undertook experiments to determine if mice with disruption (Bmal1‐KO) or mutation (Clockmut) of the circadian clock conditioned the adaptation of blood vessels to chronic disturbances. Implementing the common carotid artery ligation model of vascular remodeling, we found that Bmal1‐KO mice exhibit pathological remodeling, arterial dilatation, and thrombosis of the common carotid artery undergoing arterial ligation, identified through histomorphometric and high resolution ultrasound imaging techniques. The lumen diameter in the ligated left common carotid (LC) narrowed by 34±3.5% relative to contralateral (RC) while Bmal1‐KO were only able to adapt by a 5.2±11% reduction. In Clockmut mice, pronounced thickening occurred of the blood vessel wall after ligation, but only when the mice were housed under conditions of constant darkness (DD), not in standard light‐dark conditions, consistent with light‐cycle dependent worsening of circadian rhythms in these mice. The hyperplastic response to intraluminal wire injury of the femoral artery was also more pronounced in Bmal1‐KO and Clockmut mice relative to controls. These data suggest that the circadian clock may be an important contributing factor in the pathogenesis of vascular disease.