© 2002 by European Society of Cardiology
Copyright © 2002, European Society of Cardiology
Acute stress induces cardiac mast cell activation and histamine release, effects that are increased in Apolipoprotein E knockout mice
Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA
* Corresponding author. Tel.: +1-617-636-6866; fax: +1-617-636-2456 theoharis.theoharides{at}tufts.edu
Objectives: Cardiac mast cells have recently been found to be activated in atherosclerotic coronary arteries, but no mediator has so far been documented to be released from them, nor have they been investigated in Apolipoprotein (Apo) E knockout (k/o) mice that develop atherosclerosis. Psychological stress triggers acute coronary syndrome, while acute restraint stress stimulates rat cardiac mast cells, the main mediator of which histamine is a coronary constrictor. Here, we investigated the effect of acute stress on the activation of cardiac mast cells morphologically, as well as the levels of cardiac and serum histamine in normal and genetically deficient mice. Methods: Male, 8–14 week-old ApoE k/o mice and their corresponding control C57BL/6J mice were used. Significant reduction of cardiac histamine from 396.7±45.6 to 214.6±41.5 ng/g was observed over 120 min restraint stress with a corresponding increase in serum histamine from 126.9±4.0 to 188.4±17.3 ng/ml in C57BL mice. Cardiac mast cell activation was observed by light and electron microscopy. Both basal cardiac and serum histamine in ApoE k/o mice was significantly higher than that in C57BL mice. Although the extent of mast cell activation in ApoE k/o mice was similar to that of C57BL mice, the number of cardiac mast cells in ApoE k/o mice was 37% higher. Histamine levels were hardly detectable with or without stress in W/Wv mast cell deficient mice. Conclusions: Acute restraint stress triggered cardiac histamine release in mice that was clearly derived from mast cells, as it was absent in W/Wv mice. The high basal cardiac and serum histamine in ApoE k/o mice, along with the high number of cardiac mast cells, suggest possible ongoing cardiac mast cell activation that may participate in atherosclerosis. These results may possibly help better understand stress-related cardiovascular pathology.
KEYWORDS Atherosclerosis; Coronary disease; Cytokines; Ischemia; Vasoactive agents
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  P. A. VanderLaan and C. A. Reardon Thematic review series: The Immune System and Atherogenesis. The unusual suspects:an overview of the minor leukocyte populations in atherosclerosis J. Lipid Res., May 1, 2005; 46(5): 829 - 838. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Li, J. F. Wen, J. Y. Jin, H. Jin, H. S. Ann, S. Z. Kim, S. H. Kim, H. S. Lee, and K. W. Cho Histamine inhibits atrial myocytic ANP release via H2 receptor-cAMP-protein kinase signaling Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2003; 285(2): R380 - R393. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Huang, X. Pang, K. Karalis, and T. C. Theoharides Stress-induced interleukin-6 release in mice is mast cell-dependent and more pronounced in Apolipoprotein E knockout mice Cardiovasc Res, July 1, 2003; 59(1): 241 - 249. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Li, C. Burkhardt, U.-R. Heinrich, I. Brausch, N. Xia, and U. Forstermann Histamine Upregulates Gene Expression of Endothelial Nitric Oxide Synthase in Human Vascular Endothelial Cells Circulation, May 13, 2003; 107(18): 2348 - 2354. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. H Chester Mast cells feel the strain Cardiovasc Res, July 1, 2002; 55(1): 13 - 15. [Full Text] [PDF]
|
|