Cardiac mast cells have been implicated in the pathophysiology of cardiovascular disorders. We are the first laboratory to clearly identify a functional role for cardiac mast cells in the ventricular remodeling contributing to the development of congestive heart failure. Previously, we demonstrated a significant increase in cardiac mast cells as early as 12 hr in the left ventricle (LV), which persists for one week. A subsequently rise in mast cell numbers occurs by 5 weeks post fistula lasting for 2 weeks. Each sequential time point may contain immature and undifferentiated mast cells, which have been previously demonstrated in the normal heart. We recently demonstrated a significant shift in maturation/differentiation of peritoneal and cardiac mast cells following 24 hr of biventricular volume overload in the rat. We intend to characterize the morphology, function, and development of precursor mast cells, and to assess the effect of terminally differentiated cell products on precursor cells. We hypothesize that the acute rise in cardiac mast cells following biventricular volume overload is due to maturation and differentiation of resident cardiac mast cells. Second, these precursor mast cells may possess the ability to proliferate, degranulate, and contain similar developmental markers to the """"""""Connective Tissue-Like"""""""" mast cell. Thirdly, a factor released from terminally differentiated mast cells may bring about a shift in maturation and differentiation locally or remotely. Finally, to identify the role of differentially developed mast cells during ventricular remodeling. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32HL072566-02
Application #
6690003
Study Section
Special Emphasis Panel (ZRG1-F10 (20))
Program Officer
Commarato, Michael
Project Start
2003-01-06
Project End
2006-01-05
Budget Start
2004-01-06
Budget End
2005-01-05
Support Year
2
Fiscal Year
2004
Total Cost
$48,928
Indirect Cost
Name
Auburn University at Auburn
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
066470972
City
Auburn University
State
AL
Country
United States
Zip Code
36849
Brower, Gregory L; Gardner, Jason D; Forman, Mary F et al. (2006) The relationship between myocardial extracellular matrix remodeling and ventricular function. Eur J Cardiothorac Surg 30:604-10
Forman, M F; Brower, G L; Janicki, J S (2006) Rat cardiac mast cell maturation and differentiation following acute ventricular volume overload. Inflamm Res 55:408-15
Janicki, Joseph S; Brower, Gregory L; Gardner, Jason D et al. (2006) Cardiac mast cell regulation of matrix metalloproteinase-related ventricular remodeling in chronic pressure or volume overload. Cardiovasc Res 69:657-65
Forman, M F; Brower, G L; Janicki, J S (2004) Spontaneous histamine secretion during isolation of rat cardiac mast cells. Inflamm Res 53:453-7