Persistently increased systemic, but not cardiac-specific, adhesion molecule expression and coronary endothelial dysfunction in human cardiac allografts.
BACKGROUND
Adhesion molecules are involved in inflammatory processes that alter endothelial function and lead to impairment of coronary vasomotor function. We studied a possible relationship between systemic expression, cardiac-specific expression, or both of P-selectin and intercellular adhesion molecule 1 and coronary vasomotor function both 1 and 12 months after heart transplantation in human subjects.


METHODS
The expression of endomyocardial and soluble forms of P-selectin and intercellular adhesion molecule 1, as well as levels of tumor necrosis factor alpha, were determined in aortic and coronary sinus blood samples 1, 6, and 12 months after heart transplantation in 42 transplant recipients and 20 age-matched, nontransplanted control subjects. In addition, both endothelium-dependent (acetylcholine) and endothelium-independent (adenosine) coronary vasomotor function were assessed by using a Doppler flow wire and quantitative coronary angiography 1 and 12 months after heart transplantation.


RESULTS
Adhesion molecules were highly expressed 1 month after heart transplantation and remained at high levels 12 months after heart transplantation when compared with levels in nontransplanted control subjects. No cardiac-specific expression or release of P-selectin or intercellular adhesion molecule 1 was observed. There was a significant inverse correlation between coronary vasomotor function and soluble adhesion molecule expression both 1 and 12 months after heart transplantation.


CONCLUSIONS
Persistently high levels of circulating adhesion molecules are of systemic, but not cardiac-specific, origin and reflect a chronic inflammatory state throughout the first year after heart transplantation. This is associated with impairment of coronary vasomotor function, an early and potentially reversible step in the process of atherothrombosis and transplant coronary artery disease.
Wildhirt
Stephen M
SM
Department of Cardiovascular Surgery, German Heart Center Munich, Technical University of Munich, Munich, Germany. wildhirt@gmx.net
Schulze
Costas
C
Conrad
Nicole
N
Bauernschmitt
Robert
R
Lange
Rüdiger
R
von Scheidt
Wolfgang
W
D003331:Coronary Vessels / Q000378:metabolism* / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000503:physiopathology*; D005260:Female; D016027:Heart Transplantation; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000096:biosynthesis*; D013997:Time Factors
D019007:P-Selectin; D018799:Intercellular Adhesion Molecule-1