Intimal hyperplasia and expression of transforming growth factor-beta1 in saphenous veins and internal mammary arteries before coronary artery surgery.
BACKGROUND
The development of fibromuscular intimal hyperplasia and subsequent graft failure remains an urgent problem in cardiac surgery. Transforming growth factor-beta1 (TGF-beta1) is involved in the pathogenesis of arteriosclerosis through induction of extracellular matrix proteins. We tested the hypothesis that intimal hyperplasia is already present in human saphenous veins and left internal mammary arteries before coronary artery bypass surgery and is associated with an increased expression of TGF-beta1.


METHODS
Forty-six segments of saphenous veins and 27 of left internal mammary arteries were collected from 50 patients undergoing coronary artery bypass surgery. Morphometric analysis was performed by microscopic computer analysis. Immunohistochemistry was performed with antibodies directed against TGF-beta1, its latent binding protein (LTBP-1) and its type 2 receptor (RII).


RESULTS
The incidence of intimal hyperplasia was significantly higher in saphenous veins (67.4%) than in mammary arteries (29.6%; p < 0.05). Saphenous veins and mammary arteries with intimal hyperplasia expressed more TGF-beta1 (endothelial and intimal layers) and LTBP-1 (intimal and medial layers) when compared with corresponding vessels without hyperplasia (both groups p < 0.05). Endothelial and intimal RII expression was significantly higher in saphenous veins with intimal hyperplasia as compared with saphenous veins without hyperplasia (p < 0.05). Transforming growth factor-beta1 staining in the intima correlated with the presence of an intimal hyperplasia in saphenous veins (rho = 0.317) and mammary arteries (rho = 0.428).


CONCLUSIONS
Local TGF-beta1 expression is associated with the presence of intimal hyperplasia in the examined vessels. Preexisting intimal hyperplasia is more prevalent and serious in saphenous veins than in left internal mammary arteries, giving further explanation to the superior long-term results of left internal mammary grafts.
Department of Cardiac Surgery, University Hospital Ulm, Ulm, Germany.
Reinhard
R
Friedl
Jun
J
Li
Bernd
B
Schumacher
Hartmut
H
Hanke
Johannes
J
Waltenberger
Andreas
A
Hannekum
Sylvia
S
Stracke
D000368:Aged; D001161:Arteriosclerosis / Q000378:metabolism / Q000473:pathology; D001026:Coronary Artery Bypass; D005260:Female; D006801:Humans; D006965:Hyperplasia; D007387:Internal Mammary-Coronary Artery Anastomosis; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis; D053779:Latent TGF-beta Binding Proteins; D008297:Male; D008323:Mammary Arteries / Q000378:metabolism / Q000473:pathology* / Q000637:transplantation; D008875:Middle Aged; D009928:Organ Specificity; D011446:Prospective Studies; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis; D012501:Saphenous Vein / Q000378:metabolism / Q000473:pathology* / Q000637:transplantation; D013997:Time Factors; D020858:Tissue and Organ Harvesting; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000096:biosynthesis*; D053773:Transforming Growth Factor beta1; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology*; D017540:Tunica Media / Q000378:metabolism / Q000473:pathology
D047908:Intracellular Signaling Peptides and Proteins; C509032:LTBP1 protein, human; D053779:Latent TGF-beta Binding Proteins; D018125:Receptors, Transforming Growth Factor beta; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II