Journal
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
Volume 43, Issue 6, Pages 744-753Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.yjmcc.2007.08.018
Keywords
chronobiology; gene expression; hypoxia; ischemia; metabolism
Categories
Funding
- FIC NIH HHS [R03 TW007344, TW 007344] Funding Source: Medline
- NHLBI NIH HHS [HL 074259, HL 074237, R01 HL074259, P01 HL074237, R01 HL074259-06] Funding Source: Medline
Ask authors/readers for more resources
The intracellular circadian clock consists of a series of transcriptional modulators that together allow the cell to perceive the time of day. Circadian clocks have been identified within various components of the cardiovascular system (e.g. cardiomyocytes, vascular smooth muscle cells) and possess the potential to regulate numerous aspects of cardiovascular physiology and pathophysiology. The present study tested the hypothesis that ischemia/reperfusion (I/R; 30 min occlusion of the rat left main coronary artery in vivo) alters the circadian clock within the ischemic, versus non-ischemic, region of the heart. Left ventricular anterior (ischemic) and posterior (non-ischemic) regions were isolated from I/R, sham-operated, and naive rats over a 24-h period, after which mRNAs encoding for both circadian clock components and known clock-controlled genes were quantified. Circadian clock gene oscillations (i.e. peak-to-trough fold differences) were rapidly attenuated in the I/R, versus the non-ischemic, region. Consistent with decreased circadian clock output, we observe a rapid induction of E4BP4 in the ischemic region of the heart at both the mRNA and protein levels. In contrast with I/R, chronic (1 week) hypobaric chamber-induced hypoxia did not attenuate oscillations in circadian clock genes in either the left or right ventricle of the rat heart. In conclusion, these data show that in a rodent model of myocardial I/R, circadian clocks within the ischemic region become rapidly impaired, through a mechanism that appears to be independent of hypoxia. (c) 2007 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available