Endothelin-1 mediates cardiac mast cell degranulation, matrix metalloproteinase activation, and myocardial remodeling in rats

American Journal of Physiology. Heart and Circulatory Physiology
David B MurrayJoseph S Janicki

Abstract

The objective of this study was to determine whether elevated circulating levels of endothelin (ET)-1 are capable of mediating left ventricular (LV) mast cell degranulation and thereby induce matrix metalloproteinase (MMP) activation. After the administration of 20 pg/ml ET-1 to blood-perfused isolated rat hearts, LV tissue was analyzed for signs of mast cell degranulation and MMP activation. Relative to control, ET-1 produced extensive mast cell degranulation as well as a significant increase in myocardial water content (78.8 +/- 1.5% vs. 74.2 +/- 2.2%, P <0.01), a marked 107% increase in MMP-2 activity (P <0.05), and a substantial decrease in collagen volume fraction (0.69 +/- 0.09% vs. 0.99 +/- 0.04%, P <0.001). Although the myocardial edema would be expected to increase ventricular stiffness, compliance was not altered, and moderate ventricular dilatation was observed (end-diastolic volume at end-diastolic pressure of 0 mmHg of 330.2 +/- 22.1 vs. 298.9 +/- 17.4 microl in ET-1 treated vs. control, respectively, P=0.07). Additionally, pretreatment with the mast cell stabilizer nedocromil prevented ET-1-induced changes in MMP-2 activity, myocardial water content, collagen volume fraction, and end-diastolic volume. These findin...Continue Reading

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Citations

Aug 26, 2010·Cardiovascular Research·Scott P LevickJoseph S Janicki
Nov 26, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Jason D GardnerJoseph S Janicki
May 12, 2009·American Journal of Physiology. Heart and Circulatory Physiology·David B MurrayJoseph S Janicki
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Jan 8, 2008·American Journal of Physiology. Heart and Circulatory Physiology·David B MurrayJoseph S Janicki
Feb 22, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Amanda L ChanceyJoseph S Janicki
Apr 17, 2007·American Journal of Physiology. Heart and Circulatory Physiology·David B MurrayJoseph S Janicki
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