Cardiac hypertrophy after transplantation is associated with persistent expression of tumor necrosis factor-alpha.
BACKGROUND
The mechanisms that contribute to cardiac allograft hypertrophy are not known; however, the rapid progression and severity of hypertrophy suggest that nonhemodynamic factors may play a contributory role. Tumor necrosis factor-alpha (TNF-alpha) is a cytokine produced in cardiac allografts and capable of producing hypertrophy and fibrosis; therefore, we suggest that TNF-alpha may play a contributory role. Accordingly, the aims of our study were to define the role of systemic hypertension in the development of hypertrophy, characterize the histological determinants of hypertrophy, and characterize the expression of myocardial TNF-alpha after heart transplantation.


RESULTS
To separate the effect of hypertension from immune injury in the development of cardiac allograft hypertrophy, we measured the gain in left ventricular mass by 2D echocardiography in heart transplant recipients and lung transplant recipients who developed similar rates of systemic hypertension. The gain in left ventricular mass was 73% in heart transplant recipients and 7% in lung transplant recipients (P<0.0001). By comparing myocardial samples obtained during the first week after transplant and at 1 year, we found that there was a significant increase in total collagen content (P<0.0001), collagen I (P<0.0001), collagen III (P<0.0001), and myocyte size (P<0.0001). These changes were associated with persistent myocardial TNF-alpha expression.


CONCLUSIONS
We suggest that the contribution of hypertension to cardiac allograft hypertrophy is minimal and that persistent intracardiac expression of TNF-alpha may contribute to the development of cardiac allograft hypertrophy.
Stetson
S J
SJ
Department of Medicine, The DeBakey Heart Center, The Winters Center for Heart Failure Research, Baylor College of Medicine, Houston, Texas, USA.
Perez-Verdia
A
A
Mazur
W
W
Farmer
J A
JA
Koerner
M M
MM
Weilbaecher
D G
DG
Entman
M L
ML
Quiñones
M A
MA
Noon
G P
GP
Torre-Amione
G
G
D006332:Cardiomegaly / Q000378:metabolism* / Q000473:pathology; D003094:Collagen / Q000378:metabolism; D005260:Female; D006084:Graft Rejection / Q000378:metabolism / Q000473:pathology; D016027:Heart Transplantation; D006352:Heart Ventricles / Q000737:chemistry / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D013599:Systole / Q000502:physiology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D014409:Tumor Necrosis Factor-alpha; D003094:Collagen